Method for producing pyridazinone compounds and intermediate thereof

ABSTRACT

The present invention relates to a novel method for producing a pyridazinone compound and an intermediate
         thereof as shown in the following scheme:       

                         
wherein the symbols are as defined in the specification.

TECHNICAL FIELD

The present invention relates to a method for producing pyridazinonecompounds and intermediates thereof.

BACKGROUND ART

A certain pyridazinone compound is known to be useful as an activeingredient in a medicine or pesticide or be used as an intermediate of amedicine or pesticide (see, Patent Literatures 1-10).

CITATION LIST Patent Literature

-   Patent Literature 1: WO 2007-119434-   Patent Literature 2: WO 2009-035150-   Patent Literature 3: WO 2009-086041-   Patent Literature 4: WO 2007-080720-   Patent Literature 5: WO 2009-090039-   Patent Literature 6: EP 835 865 A-   Patent Literature 7: WO 2004-058729-   Patent Literature 8: WO 2005-007632-   Patent Literature 9: WO 2005-077915-   Patent Literature 10: JP-A-2009-215312

SUMMARY OF INVENTION Technical Problem

The present invention provides a novel method for producing pyridazinonecompounds and the intermediates thereof.

Solution to Problem

The present invention relates to a novel method for producingpyridazinone compounds and the intermediates thereof. The summary isshown below:

wherein the symbols in each formula are defined as follows:

R¹ represents hydrogen, a C1-C6 alkyl group, or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and    -   the phenyl group may optionally have one or more substituents        selected from Group 1, provided that when it has two or more        substituents, then the substituents may be same or different;    -   the Group 1 consists of halogen, a cyano group, a nitro group, a        C1-C6 alkyl group, a C1-C6 alkoxy group, and a (C1-C6        alkoxy)C1-C6 alkyl group;    -   in the Group 1, the C1-C6 alkyl group, the C1-C6 alkoxy group,        and the (C1-C6 alkoxy)C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different;

R² represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkylgroup, a (C1-C6 alkylthio)C1-C6 alkyl group, a (C1-C6alkylsulfinyl)C1-C6 alkyl group, a (C1-C6 alkylsulfonyl)C1-C6 alkylgroup, a phenyl group, or a 5- or 6-membered heteroaryl group;

-   -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkyl group,        the (C1-C6 alkylsulfinyl)C1-C6 alkyl group, and the (C1-C6        alkylsulfonyl)C1-C6 alkyl group may be optionally substituted        with one or more halogens, provided that when they are        substituted with two or more halogens, then the halogens may be        same or different,    -   the phenyl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group 2,        provided that when they have two or more substituents, then the        substituents may be same or different,    -   the Group 2 consists of halogen, a cyano group, a nitro group, a        formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a        (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6        alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthio        group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group,        a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6        cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, and a tri(C1-C6        alkyl)silyl group;    -   in the Group 2, the C1-C6 alkyl group, the C1-C6 alkoxy group,        the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group,        the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the C1-C6        alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

R³ represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkylgroup, a (C1-C6 alkylthio)C1-C6 alkyl group, a C1-C6 alkylsulfonylgroup, a (C1-C6 alkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a(C1-C6 alkylamino)Carbonyl group, a di(C1-C6 alkyl)aminocarbonyl group,a (C3-C6 cycloalkylamino)carbonyl group, a phenyl group, a benzyl group,or a phenylsulfonyl group;

-   -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkyl group,        the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,        and the (C1-C6 alkoxy)carbonyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different; and    -   the phenyl group, the benzyl group, and the phenylsulfonyl group        may optionally have one or more substituents selected from Group        3, provided that when they have two or more substituents, then        the substituents may be same or different;    -   the Group 3 consists of halogen, a C1-C6 alkyl group, a C1-C6        alkoxy group, and a (C1-C6 alkoxy)C1-C6 alkyl group;    -   in the Group 3, the C1-C6 alkyl group, the C1-C6 alkoxy group,        and the (C1-C6 alkoxy)C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different;

R⁵ represents a C1-C6 alkyl group or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and    -   the phenyl group may optionally have one or more substituents        selected from Group 5, provided that when it has two or more        substituents, then the substituents may be same or different,    -   the Group 5 consists of halogen, a C1-C6 alkyl group and a C1-C6        alkoxy group;    -   in the Group 5, the C1-C6 alkyl group and the C1-C6 alkoxy group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

G represents a C6-C10 aryl group, a 5- or 6-membered heteroaryl group,or an 8- to 10-membered fused heteroaryl group;

-   -   wherein the C6-C10 aryl group, the 5- or 6-membered heteroaryl        group, and the 8- to 10-membered fused heteroaryl group may        optionally have one or more substituents selected from Group R⁴,        provided that when they have two or more substituents, then the        substituents may be same or different,    -   the Group R⁴ consists of halogen, a cyano group, a nitro group,        a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a        (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6        alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthio        group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group,        a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6        cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, a tri(C1-C6        alkyl)silyl group, a C6-C10 aryl group, and a 5- or 6-membered        heteroaryl group;    -   in the Group R⁴, the C1-C6 alkyl group, the C1-C6 alkoxy group,        the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group,        the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the C1-C6        alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and    -   in the Group R⁴, the C6-C10 aryl group and the 5- or 6-membered        heteroaryl group may optionally have one or more substituents        selected from Group 4, provided that when they have two or more        substituents, then the substituents may be same or different;    -   the Group 4 consists of halogen, a cyano group, a nitro group, a        formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a        (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6        alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthio        group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group,        a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6        cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, and a tri(C1-C6        alkyl)silyl group;    -   in the Group 4, the C1-C6 alkyl group, the C1-C6 alkoxy group,        the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group,        the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the C1-C6        alkynyl group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

n represents an integer of 0, 1 or 2;

V represents an integer of 1 or 2;

M represents an alkali metal when V is an integer of 1, and M representsan alkali earth metal when V is an integer of 2;

X¹ represents fluorine, chlorine, bromine, or iodine;

X² represents chlorine, bromine, or iodine;

Y represents a C1-C6 alkyl group wherein the C1-C6 alkyl group may beoptionally substituted with one or more halogens, provided that when itis substituted with two or more halogens, then the halogens may be sameor different;

R^(3B) represents a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a (C1-C6alkylthio)C1-C6 alkyl group, a C1-C6 alkylsulfonyl group, a (C1-C6alkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a di(C1-C6alkyl)aminocarbonyl group, a benzyl group, or a phenylsulfonyl group;

-   -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        (C1-C6 alkylthio)C1-C6 alkyl group, the C1-C6 alkylsulfonyl        group, the (C1-C6 alkyl)carbonyl group, and the (C1-C6        alkoxy)carbonyl group may be optionally substituted with one or        more halogens, provided that when they are substituted with two        or more halogens, then the halogens may be same or different;        and the benzyl group, and the phenylsulfonyl group may        optionally have one or more substituents selected from Group 3B,        provided that when they have two or more substituents, then the        substituents may be same or different,    -   the Group 3B consists of halogen, a C1-C6 alkyl group, a C1-C6        alkoxy group, and a (C1-C6 alkoxy)C1-C6 alkyl group;    -   in the Group 3B, the C1-C6 alkyl group, the C1-C6 alkoxy group,        and the (C1-C6 alkoxy)C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different;

G^(B) represents a phenyl group;

-   -   wherein the phenyl group may optionally have one or more        substituents selected from R^(4-B), provided that when they have        two or more substituents, then the substituents may be same or        different;    -   the Group R^(4-B) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4-B), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl) carbonyl group, the        (C3-C6 cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group        4-B, provided that when they have two or more substituents, then        the substituents may be same or different;    -   the Group 4-B consists of halogen, a cyano group, a nitro group,        a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a        (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6        alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthio        group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group,        a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6        cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, and a tri(C1-C6        alkyl)silyl group;    -   in the Group 4-B, the C1-C6 alkyl group, the C1-C6 alkoxy group,        the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group,        the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the C1-C6        alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl) carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

R¹⁰ and R¹¹ may be same or different, and each represents hydrogen, aC1-C6 alkyl group, a C3-C6 cycloalkyl group or a phenyl group, or R¹⁰and R¹¹ may be combined to form 5- or 6-membered cyclic group with acarbon atom which is bonded with R¹⁰ and R¹¹,

-   -   wherein the C1-C6 alkyl group and the C3-C6 cycloalkyl group may        be optionally substituted with one or more halogens, provided        that when it is substituted with two or more halogens, then the        halogens may be same or different; and the phenyl group may        optionally have one or more substituents selected from Group 10,        provided that when it has two or more substituents, then the        substituents may be same or different;    -   the Group 10 consists of halogen, a C1-C6 alkyl group and a        C1-C6 alkoxy group; and

L represents halogen, a C1-C6 alkylsulfonyloxy group or a C1-C6alkoxysulfonyloxy group.

Effects of Invention

According to the present invention, various pyridazinone compounds whichare useful as an active ingredient in a medicine or pesticide can beprepared.

In particular, the present invention provides:

[1] A method for producing a compound of the formula (1):

which comprises reacting a compound of the formula (2):

with a compound of the formula (3):M(OR¹)_(v)  (3);wherein the symbols in the formulae (1), (2) and (3) are as definedabove.[2] The method according to the above [1], wherein n is an integer of 2.[3] The method according to the above [1] or [2], wherein G is a phenylgroup wherein the phenyl group may optionally have one or moresubstituents selected from the Group R⁴, provided that when it has twoor more substituents, then the substituents may be same or different.[4] The method according to any one of the above [1]-[3], wherein theGroup R⁴ is Group R⁴⁻¹;

wherein the Group R⁴⁻¹ consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkylgroup, a C2-C6 alkynyl group, and a phenyl group;

in the Group R⁴⁻¹, the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent; and

the phenyl group may optionally have one or more substituents selectedfrom Group 4-1, provided that when it has two or more substituents, thenthe substituents may be same or different;

the Group 4-1 consists of halogen and a C1-C6 alkyl group;

in the Group 4-1, the C1-C6 alkyl group may be optionally substitutedwith one or more halogens, provided that when it is substituted with twoor more halogens, then the halogens may be same or different.

[5] The method according to the above [4], wherein R¹ is hydrogen, aC1-C6 alkyl group or a phenyl group,

R² is hydrogen, a C1-C6 alkyl group or a phenyl group wherein the C1-C6alkyl group may be optionally substituted with one or more halogens,provided that when it is substituted with two or more halogens, then thehalogens may be same or different, and the phenyl group may optionallyhave one or more halogens, provided that when it has two or morehalogens, then the halogens may be same or different;

R³ is hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkyl group,or a benzyl group wherein the C1-C6 alkyl group, and the (C1-C6alkoxy)C1-C6 alkyl group may be optionally substituted with one or morehalogens, provided that when they are substituted with two or morehalogens, then the halogens may be same or different; and the benzylgroup may optionally have one or more substituents selected from thegroup consisting of halogen, a C1-C6 alkyl group, and a C1-C6 alkoxygroup, provided that when they have two or more substituents, then thesubstituents may be same or different;

R⁵ is a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when it is substituted with two or more halogens, then the halogensmay be same or different; and the phenyl group may optionally have oneor more a C1-C6 alkyl group, provided that when it has two or more C1-C6alkyl groups, then the C1-C6 alkyl groups may be same or different; and

G is a phenyl group, a pyridyl group, an indolyl group or a pyrazolylgroup wherein the phenyl group, the pyridyl group, the indolyl group andthe pyrazolyl group may optionally have one or more substituentsselected from Group R⁴⁻¹, provided that when they have two or moresubstituents, then the substituents may be same or different.

[6] The method according to the above [1], wherein R¹ is hydrogen, amethyl group, an ethyl group, a n-butyl group or a phenyl group, R² is amethyl group, a 4-fluorophenyl group or a trifluoromethyl group, R³ is amethyl group or a benzyl group, R⁵ is a methyl group or a 4-methylphenylgroup, and G is a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a 1-methylindol-3-yl group or a2,6-diethyl-4-methylphenyl group.[7] A method for producing a compound of the formula (1):

which comprises the steps of:reacting a compound of the formula (4):

with a base to obtain a compound of the formula (2):

andreacting the compound of the formula (2) with a compound of the formula(3):M(OR¹)_(v)  (3);wherein the symbols in the formulae (1), (2), (3) and (4) are as definedabove.[8] A method for producing a compound of the formula (2):

which comprises reacting a compound of the formula (4):

with a base;wherein the symbols in the formulae (2) and (4) are as defined above.[9] The method according to the above [8], wherein G is a phenyl groupwherein the phenyl group may optionally have one or more substituentsselected from the Group R⁴, provided that when it has two or moresubstituents, then the substituents may be same or different.[10] The method according to the above [8] or [9], wherein the Group R⁴is Group R⁴⁻³;

wherein the Group R⁴⁻³ consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkylgroup, a C2-C6 alkynyl group, and a phenyl group;

in the Group R⁴⁻³, the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or m ore halogens, then the halogens may be same ordifferent; and the phenyl group may optionally have one or moresubstituents selected from Group 4-3, provided that when it has two ormore substituents, then the substituents may be same or different;

the Group 4-3 consists of halogen and a C1-C6 alkyl group;

-   -   in the Group 4-3, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different.        [11] The method according to the above [10], wherein R² is        hydrogen, a C1-C6 alkyl group or a phenyl group wherein the        C1-C6 alkyl group may be optionally substituted with one or more        halogens, provided that when it is substituted with two or more        halogens, then the halogens may be same or different, and the        phenyl group may optionally have one or more halogens, provided        that when it has two or more halogens, then the halogens may be        same or different;

R³ is hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkyl group,or a benzyl group wherein the C1-C6 alkyl group and the (C1-C6alkoxy)C1-C6 alkyl group may be optionally substituted with one or morehalogens, provided that when they are substituted with two or morehalogens, then the halogens may be same or different; and the benzylgroup may optionally have one or more substituents selected from thegroup consisting of halogen, a C1-C6 alkyl group, and a C1-C6 alkoxygroup, provided that when they have two or more substituents, then thesubstituents may be same or different;

R⁵ is a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when it is substituted with two or more halogens, then the halogensmay be same or different; and the phenyl group may optionally have aC1-C6 alkyl group, provided that when it has two or more C1-C6 alkylgroups, then the C1-C6 alkyl groups may be same or different; and

G is a phenyl group, a pyridyl group, an indolyl group or a pyrazolylgroup wherein the phenyl group, the pyridyl group, the indolyl group andthe pyrazolyl group may optionally have one or more substituentsselected from Group R⁴⁻³, provided that when they have two or moresubstituents, then the substituents may be same or different.

[12] The method according to the above [8], wherein R² is a methylgroup, a 4-fluorophenyl group or a trifluoromethyl group, R³ is a methylgroup or a benzyl group, R⁵ is a methyl group or a 4-methylphenyl group,and G is a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a 1-methylindol-3-yl group or a2,6-diethyl-4-methylphenyl group.[13] A method for producing a compound of the formula (1):

which comprises the steps of:reacting a compound of the formula (5):

with a compound of the formula (6):

to obtain a compound of the formula (4):

reacting the compound of the formula (4) with a base to obtain acompound of the formula (2):

andreacting the compound of the formula (2) with a compound of the formula(3):M(OR¹)_(v)  (3);wherein the symbols in the formulae (1), (2), (3), (4), (5) and (6) areas defined above.[14] A method for producing a compound of the formula (4):

which comprises reacting a compound of the formula (5):

with a compound of the formula (6):

wherein the symbols in the formulae (4), (5) and (6) are as definedabove.[15] The method according to the above [14], wherein G is a phenyl groupwherein the phenyl group may optionally have one or more substituentsselected from the Group R⁴, provided that when it has two or moresubstituents, then the substituents may be same or different.[16] The method according to the above [14] or [15], wherein the GroupR⁴ is Group R⁴⁻⁵;

wherein the Group R⁴⁻⁵ consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkylgroup, a C2-C6 alkynyl group, and a phenyl group;

in the Group R⁴⁻⁵, the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent; and the phenyl group may optionally have one or moresubstituents selected from Group 4-5, provided that when it has two ormore substituents, then the substituents may be same or different;

the Group 4-5 consists of halogens and a C1-C6 alkyl group;

in the Group 4-5, the C1-C6 alkyl group may be optionally substitutedwith one or more halogens, provided that when it is substituted with twoor more halogens, then the halogens may be same or different.

[17] The method according to the above [16], wherein R² is hydrogen, aC1-C6 alkyl group or a phenyl group wherein the C1-C6 alkyl group may beoptionally substituted with one or more halogens, provided that when itis substituted with two or more halogens, then the halogens may be sameor different, and the phenyl group may optionally have one or morehalogens, provided that when it has two or more halogens, then thehalogens may be same or different;

R³ is hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkyl group,or a benzyl group wherein the C1-C6 alkyl group and the (C1-C6alkoxy)C1-C6 alkyl group may be optionally substituted with one or morehalogens, provided that when they are substituted with two or morehalogens, then the halogens may be same or different; and the benzylgroup may optionally have one or more substituents selected from thegroup consisting of halogen, a C1-C6 alkyl group, and a C1-C6 alkoxygroup, provided that when it has two or more substituents, then thesubstituents may be same or different;

R⁵ is a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when it is substituted with two or more halogens, then the halogensmay be same or different; and the phenyl group may optionally have oneor more a C1-C6 alkyl group, provided that when it has two or more C1-C6alkyl groups, then the C1-C6 alkyl groups may be same or different; and

G is a phenyl group, a pyridyl group, an indolyl group or a pyrazolylgroup wherein the phenyl group, the pyridyl group, the indolyl group andthe pyrazolyl group may optionally have one or more substituentsselected from Group R⁴⁻⁵, provided that when they have two or moresubstituents, then the substituents may be same or different.

[18] The method according to the above [14], wherein R² is a methylgroup or a 4-fluorophenyl group, R³ is a methyl group, or a benzylgroup, R⁵ is a methyl group, G is a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a5-ethyl-3-(4-trifluoromethylphenyl)pyrazol-1-yl group, a1-methylindol-3-yl group or a 2,6-diethyl-4-methylphenyl group, and X¹is chlorine.[19] A method for producing a compound of the formula (1):

which comprises the steps of:reacting a compound of the formula (7):

with a compound of the formula (12):

to obtain a compound of the formula (4):

reacting the compound of the formula (4) with a base to obtain acompound of the formula (2):

andreacting the compound of the formula (2) with a compound of the formula(3):M(OR¹)_(v)  (3);wherein the symbols in the formulae (1), (2), (3), (4), (7) and (12) areas defined above.[20] A method for producing a compound of the formula (4):

which comprises reacting a compound of the formula (7):

with a compound of the formula (12):

wherein the symbols in the formulas (4), (7) and (12) are as definedabove.[21] The method according to the above [20], wherein G is a phenyl groupwherein the phenyl group may optionally have one or more substituentsselected from the Group R⁴, provided that when it has two or moresubstituents, then the substituents may be same or different.[22] The method according to the above [20] or [21], wherein the GroupR⁴ is Group R⁴⁻⁷;

wherein the Group R⁴⁻⁷ consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkylgroup, a C2-C6 alkynyl group, and a phenyl group;

in the Group R⁴⁻⁷, the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent; and the phenyl group may optionally have one or moresubstituents selected from Group 4-7, provided that when it has two ormore substituents, then the substituents may be same or different;

the Group 4-7 consists of halogen and a C1-C6 alkyl group;

in the Group 4-7, the C1-C6 alkyl group may be optionally substitutedwith one or more halogens, provided that when it is substituted with twoor more halogens, then the halogens may be same or different.

[23] The method according to the above [22], wherein R² is hydrogen or aC1-C6 alkyl group wherein the C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when it issubstituted with two or more halogens, then the halogens may be same ordifferent;

R³ is hydrogen, a C1-C6 alkyl group, or a (C1-C6 alkoxy)C1-C6 alkylgroup wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when they are substituted with two or more halogens, then thehalogens may be same or different;

R⁵ is a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when it is substituted with two or more halogens, then the halogensmay be same or different; and the phenyl group may optionally have oneor more C1-C6 alkyl groups, provided that when it has two or more C1-C6alkyl groups, then the C1-C6 alkyl groups may be same or different; and

G is a phenyl group, a pyridyl group, an indolyl group or a pyrazolylgroup wherein the phenyl group, the pyridyl group, the indolyl group andthe pyrazolyl group may optionally have one or more substituentsselected from Group R⁴⁻⁷, provided that when they have two or moresubstituents, then the substituents may be same or different.

[24] The method according to the above [20], wherein R² is a methylgroup or a trifluoromethyl group, R³ is a methyl group, R⁵ is a methylgroup or a 4-methylphenyl group, and G is a 2,4,6-triethylphenyl groupor a 2,6-diethyl-4-methylphenyl group.

When R², R³, R⁵, and G are R^(2*), R^(3*), R^(5*), and G* as definedbelow, respectively:

[25] A method for producing a compound of the formula (2*-O2):

which comprises reacting a compound of the formula (2*-O0):

or a compound of the formula (2*-O1):

with an oxidizing agent;wherein the symbols in the formulae (2*-O2), (2*-O0) and (2*-O1) aredefined as follows:

-   -   R^(2*) represents hydrogen, a C1-C6 alkyl group, a phenyl group,        or a 5- or 6-membered heteroaryl group;    -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and the phenyl group and the 5- or 6-membered        heteroaryl group may optionally have one or more substituents        selected from Group 2*, provided that when they have two or more        substituents, then the substituents may be same or different;    -   the Group 2* consists of halogen and a C1-C6 alkyl group;    -   in the Group 2*, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R^(3*) represents hydrogen, a C1-C6 alkyl group, or a (C1-C6alkoxy)C1-C6 alkyl group;

-   -   wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

R^(5*) represents a C1-C6 alkyl group or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and the phenyl group may optionally have one or more        substituents selected from Group 5*, provided that when it has        two or more substituents, then the substituents may be same or        different;    -   the Group 5* consists of halogen, a C1-C6 alkyl group, and a        C1-C6 alkoxy group;    -   in the Group 5*, the C1-C6 alkyl group and the C1-C6 alkoxy        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and

G* is a phenyl group;

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R^(4*), provided that when it        has two or more substituents, then the substituents may be same        or different;    -   the Group R^(4*) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4*), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group 4*,        provided that when they have two or more substituents, then the        substituents may be same or different;    -   the Group 4* consists of halogen, a cyano group, a nitro group,        a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a        (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6        alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthio        group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group,        a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6        cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, and a tri(C1-C6        alkyl)silyl group;    -   in the Group 4*, the C1-C6 alkyl group, the C1-C6 alkoxy group,        the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group,        the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the C1-C6        alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different.        [26] The method according to the above [25], wherein R^(2*) is        hydrogen or a C1-C6 alkyl group wherein the C1-C6 alkyl group        may be optionally substituted with one or more halogens,        provided that when it is substituted with two or more halogens,        then the halogens may be same or different;

R^(3*) is hydrogen, a C1-C6 alkyl group, or a (C1-C6 alkoxy)C1-C6 alkylgroup wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when they are substituted with two or more halogens, then thehalogens may be same or different; and

G* is a phenyl group wherein the phenyl group may optionally have one ormore substituents selected from Group R^(4*-15), provided that when ithas two or more substituents, then the substituents may be same ordifferent;

-   -   the Group R^(4*-15) consists of halogen, a cyano group, a nitro        group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6        cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group;    -   in the Group R^(4*-15), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the C3-C6 cycloalkyl group, and the C2-C6 alkynyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        phenyl group may optionally have one or more substituents        selected from Group 4*-15, provided that when it has two or more        substituents, then the substituents may be same or different;    -   the Group 4*-15 consists of halogen and C1-C6 alkyl group;    -   in the Group 4*-15, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different.        [27] The method according to the above [25], wherein R^(2*) is a        methyl group, R^(3*) is a methyl group, R^(5*) is a methyl        group, and G* is a 2,4,6-triethylphenyl group or        2,6-diethyl-4-methylphenyl group.        [28] A method of producing a compound of the formula (2*-O1):

which comprises reacting a compound of the formula (2*-O0):

with an oxidizing agent;wherein the symbols in the formulae (2*-O0) and (2*-O1) are definedabove.[29] The method according to the above [28], wherein R^(2*) is hydrogenor a C1-C6 alkyl group wherein the C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when it issubstituted with two or more halogens, then the halogens may be same ordifferent;

R^(3*) is hydrogen, a C1-C6 alkyl group, or a (C1-C6 alkoxy)C1-C6 alkylgroup wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when they are substituted with two or more halogens, then thehalogens may be same or different; and

G* is a phenyl group wherein the phenyl group may optionally have one ormore substituents selected from Group R^(4*-16), provided that when ithas two or more substituents, then the substituents may be same ordifferent;

-   -   the Group R^(4*-16) consists of halogen, a cyano group, a nitro        group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6        cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group;    -   in the Group R^(4*-16), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the C3-C6 cycloalkyl group, and the C2-C6 alkynyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        phenyl group may optionally have one or more substituents        selected from Group 4*-16, provided that when it has two or more        substituents, then the substituents may be same or different;    -   the Group 4*-16 consists of halogen and a C1-C6 alkyl group;    -   in the Group 4*-16, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different.        [30] The method according to the above [28], wherein R^(2*) is a        methyl group or a trifluoromethyl group, R^(3*) is a methyl        group, R^(5*) is a methyl group, and G* is a        2,4,6-triethylphenyl group or a 2,6-diethyl-4-methylphenyl        group.

When R², R³, R⁵, and G are R^(2-2A), R^(3-2A), R^(5-2A), and G^(2A) asdefined below, respectively:

[31] A compound of the formula (2A):

wherein the symbols in the formula (2A) are defined as follows:

R^(2-2A) represents hydrogen, a C1-C6 alkyl group, or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and the phenyl group may optionally have one or more        substituents selected from Group 2-2A, provided that when it has        two or more substituents, then the substituents may be same or        different;    -   the Group 2-2A consists of halogen and a C1-C6 alkyl group;    -   in the Group 2-2A, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R^(3-2A) represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6alkyl group, or a benzyl group;

-   -   wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        benzyl group may optionally have one or more substituents        selected from the group consisting of halogen, C1-C6 alkyl        group, and C1-C6 alkoxy group, provided that when it has two or        more substituents, then the substituents may be same or        different;

R^(5-2A) represents a C1-C6 alkyl group or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different, and    -   the phenyl group may optionally have one or more substituents        selected from Group 5-2A, provided that when it has two or more        substituents, then the substituents may be same or different;    -   the Group 5-2A consists of halogen, a C1-C6 alkyl group, and a        C1-C6 alkoxy group;    -   in the Group 5-2A, the C1-C6 alkyl group and the C1-C6 alkoxy        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

G^(2A) represents a phenyl group having one or more substituentsselected from Group R^(4-2A) or a 5- or 6-membered heteroaryl grouphaving one or more substituents selected from the Group R^(4-2A);

-   -   wherein the substituents may be same or different when the        phenyl group and 5- or 6-membered heteroaryl group have two or        more substituents; and the phenyl group has two or more        substituents when n is an integer of 0;    -   the Group R^(4-2A) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4-2A), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the (C1-C6        alkyl)carbonyl group, the (C3-C6 cycloalkyl)carbonyl group, and        the (C1-C6 alkoxy)carbonyl group may be optionally substituted        with one or more halogens, provided that when they are        substituted with two or more halogens, then the halogens may be        same or different; and the C6-C10 aryl group and the 5- or        6-membered heteroaryl group may optionally have one or more        substituents selected from Group 4-2A, provided that when they        have two or more substituents, then the substituents may be same        or different;    -   the Group 4-2A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the Group 4-2A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and

n is as defined above.

[32] The compound according to the above [31], wherein R^(2-2A) ishydrogen, a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkylgroup may be optionally substituted with one or more halogens, providedthat when it is substituted with two or more halogens, then the halogensmay be same or different, and the phenyl group may optionally have oneor more halogens, provided that when it has two or more halogens, thenthe halogens may be same or different;

R^(5-2A) is a C1-C6 alkyl group or a phenyl group wherein the C1-C6alkyl group may be optionally substituted with one or more halogens,provided that when it is substituted with two or more halogens, then thehalogens may be same or different; and the phenyl group may optionallyhave one or more C1-C6 alkyl groups, provided that when it has two ormore C1-C6 alkyl groups, then the C1-C6 alkyl groups may be same ordifferent, and

G^(2A) is a phenyl group, a pyridyl group or a pyrazolyl group whereinthe phenyl group, the pyridyl group, and the pyrazolyl group mayoptionally have one or more substituents selected from Group R^(4-2A-1),provided that when they have two or more substituents, then thesubstituents may be same or different, and the phenyl group has two ormore substituents when n is an integer of 0;

-   -   the Group R^(4-2A-1) consists of halogen, a cyano group, a nitro        group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6        cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group;    -   in the Group R^(4-2A-1), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the C3-C6 cycloalkyl group, and the C2-C6 alkynyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        phenyl group may optionally have one or more substituents        selected from Group 4-2A-1, provided that when it has two or        more substituents, then the substituents may be same or        different;    -   the Group 4-2A-1 consists of halogen and a C1-C6 alkyl group;    -   in the Group 4-2A-1, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different.        [33] The compound according to the above [31], wherein R^(2-2A)        is a methyl group, a 4-fluorophenyl group, or a trifluoromethyl        group, R^(3-2A) is a methyl group or a benzyl group, R^(5-2A) is        a methyl group or a 4-methylphenyl group, and G^(2A) is a        2,4,6-triethylphenyl group, a 2-ethyl-5-(4-chlorophenyl)phenyl        group or a 2,6-diethyl-4-methylphenyl group.

When R², R³, R⁵, and G are R^(2-4A), R^(3-4A), R^(5-4A), and G^(4A) asdefined below, respectively:

[34] A compound of the formula (4A):

wherein the symbols in the formula (4A) are defined as follows:

R^(2-4B) represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6cycloalkyl group, a (C1-C6 alkylthio)C1-C6 alkyl group, a (C1-C6alkylsulfinyl)C1-C6 alkyl group, a (C1-C6 alkylsulfonyl)C1-C6 alkylgroup, a phenyl group, or a 5- or 6-membered heteroaryl group;

-   -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkyl group,        the (C1-C6 alkylsulfinyl)C1-C6 alkyl group, and the (C1-C6        alkylsulfonyl)C1-C6 alkyl group may be optionally substituted        with one or more halogens, provided that when they are        substituted with two or more halogens, then the halogens may be        same or different, the phenyl group and the 5- or 6-membered        heteroaryl group may optionally have one or more substituents        selected from Group 2-4A, provided that when they have two or        more substituents, then the substituents may be same or        different;    -   the Group 2-4A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the Group 2-4A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;    -   R^(3-4B) represents hydrogen, a C1-C6 alkyl group, a (C1-C6        alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl        group, a C3-C6 cycloalkyl group, a (C1-C6 alkylthio)C1-C6 alkyl        group, a C1-C6 alkylsulfonyl group, a (C1-C6 alkyl)carbonyl        group, a (C1-C6 alkoxy)carbonyl group, a (C1-C6        alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl group,        a (C3-C6 cycloalkylamino)carbonyl group, a phenyl group, a        benzyl group, or a phenylsulfonyl group;    -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkyl group,        the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,        and the (C1-C6 alkoxy)carbonyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different; and the phenyl group, the benzyl group,        and the phenylsulfonyl group may optionally have one or more        substituents selected from Group 3-4A, provided that when they        have two or more substituents, then the substituents may be same        or different;    -   the Group 3-4A consists of halogen, a C1-C6 alkyl group, a C1-C6        alkoxy group, and a (C1-C6 alkoxy)C1-C6 alkyl group;    -   in the Group 3-4A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, and the (C1-C6 alkoxy)C1-C6 alkyl group may be optionally        substituted with one or more halogens provided that when they        are substituted with two or more halogens, then the halogens may        be same or different;

R^(5-4A) represents a C1-C6 alkyl group or a phenyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and the phenyl group may optionally have one or more        substituents selected from Group 5-4A, provided that when it has        two or more substituents, then the substituents may be same or        different;    -   the Group 5-4A consists of halogen, a C1-C6 alkyl group, and a        C1-C6 alkoxy group;    -   in the Group 5-4A, the C1-C6 alkyl group, and the C1-C6 alkoxy        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;

G^(4B) represents a C6-C10 aryl group, a 5- or 6-membered heteroarylgroup, or an 8- or 10-membered fused heteroaryl group;

-   -   wherein the C6-C10 aryl group, the 5- or 6-membered heteroaryl        group, and the 8- to 10-membered fused heteroaryl group may        optionally have one or more substituents selected from Group        R^(4-4B), provided that when they have two or more substituents,        then the substituents may be same or different;    -   the Group R^(4-4B) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4-4A), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group        4-4A, provided that when they have two or more substituents,        then the substituents may be same or different;    -   the Group 4-4A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the group 4-4A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and

n is as defined above.

[35] The compound according to the above [34], wherein G^(4A) is aphenyl group wherein the phenyl group may optionally have one or moresubstituents selected from the Group R^(4-4A), provided that when it hastwo or more substituents, then the substituents may be same ordifferent.[36] The compound according to the above [34] or [35], wherein the GroupR^(4-4A) is Group R^(4-4A-1);

wherein the Group R^(4-4A-1) consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkylgroup, a C2-C6 alkynyl group, and a phenyl group;

in the Group R^(4-4A-1), the C1-C6 alkyl group, the C1-C6 alkoxy group,the C3-C6 cycloalkyl group, and the C2-C6 alkynyl group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; and the phenyl group may optionally have one or moresubstituents selected from Group 4-4A-1, provided that when it has twoor more substituents, then the substituents may be same or different;

-   -   the Group 4-4A-1 consists of halogen and a C1-C6 alkyl group;

in the Group 4-4A-1, the C1-C6 alkyl group may be optionally substitutedwith one or more halogens, provided that when it is substituted with twoor more halogens, then the halogens may be same or different.

[37] The compound according to the above [36], wherein R^(2-4A) ishydrogen or a C1-C6 alkyl group wherein the C1-C6 alkyl group may beoptionally substituted with one or more halogens, provided that when itis substituted with two or more halogens, then the halogens may be sameor different;

R^(3-4A) is hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, or a benzyl group wherein the C1-C6 alkyl group and the (C1-C6alkoxy)C1-C6 alkyl group may be optionally substituted with one or morehalogens, provided that when they are substituted with two or morehalogens, then the halogens may be same or different; and the benzylgroup may optionally have one or more substituents selected from thegroup consisting of halogen, a C1-C6 alkyl group, and a C1-C6 alkoxygroup, provided that when it has two or more substituents, then thesubstituents may be same or different;

R^(5-4A) is a C1-C6 alkyl group or a phenyl group wherein the C1-C6alkyl group may be optionally substituted with one or more halogens,provided that when it is substituted with two or more halogens, then thehalogens may be same or different; and the phenyl group has one or moreC1-C6 alkyl groups, provided that when it has two or more C1-C6 alkylgroups, then the C1-C6 alkyl groups may be same or different; and

G^(4A) is a phenyl group, a pyridyl group, an indolyl group or apyrazolyl group wherein the phenyl group, the pyridyl group, the indolylgroup and the pyrazolyl group may optionally have one or moresubstituents selected from Group R^(4-4A-1), provided that when theyhave two or more substituents, then the substituents may be same ordifferent;

[38] The compound according to the above [34], wherein R^(2-4A) is amethyl group, a 4-fluorophenyl group or a trifluoromethyl group,R^(3-4A) is a methyl group or a benzyl group, R^(5-4A) is a methyl groupor a 4-methylphenyl group, and G^(4A) is a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a5-ethyl-3-(4-trifluoromethylphenyl)pyrazol-1-yl group, a1-methylindol-3-yl group or a 2,6-diethyl-4-methylphenyl group.

When R², R³, and R⁵ are R^(2-5A), R^(3-5A), and R^(5-5A) as definedbelow, respectively:

[39] A compound of the formula (5A):

wherein the symbols in the formula (5A) are defined as follows:

R^(2-5A) represents hydrogen, a C1-C6 alkyl group, a phenyl group, or a5- or 6-membered heteroaryl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and the phenyl group and the 5- or 6-membered        heteroaryl group may optionally have one or more substituents        selected from Group 2-5A, provided that when they have two or        more substituents, then the substituents may be same or        different;    -   the Group 2-5A consists of halogen and a C1-C6 alkyl group;    -   in the Group 2-5A, the C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R^(3-5A) represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6alkyl group, or a benzyl group;

-   -   wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        benzyl group may optionally have one or more substituents        selected from the group consisting of halogen, a C1-C6 alkyl        group, and a C1-C6 alkoxy group, provided that when it has two        or more substituents, then the substituents may be same or        different;

R^(5-5A) represents a C1-C6 alkyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different; and

n is a defined above.

[40] The compound according to the above [39], wherein R^(2-5A) is amethyl group or a 4-fluorophenyl group, R^(3-5A) is a methyl group or abenzyl group, and R^(5-5A) is a methyl group.

When G and X¹ are G^(6A) and X^(1-6A) as defined below, respectively:

[41] A compound of the formula (6A):

wherein the symbols in the formula (6A) are defined as follows:

G^(6A) represents a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a5-ethyl-3-(4-trifluoromethylphenyl)pyrazol-1-yl group, a1-methylindol-3-yl group or a 2,6-diethyl-4-methylphenyl group; and

X^(1-6A) represents chlorine.

When G is G^(8A) as defined below, respectively:

[42] A compound of the formula (8A):

wherein G^(8A) represents a 2,4,6-triethylphenyl group or a2,6-diethyl-4-methylphenyl group.

When G and Y are G^(9A) and Y^(9A) as defined below, respectively:

[43] A compound of the formula (9A):

wherein the symbols in the formula (9A) are defined as follows:

G^(9A) represents a 2,4,6-triethylphenyl group or a2,6-diethyl-4-methylphenyl group; and

Y^(9A) represents a C1-C6 alkyl group;

-   -   wherein the C1-C6 alkyl group may be optionally substituted with        one or more halogens, provided that when it is substituted with        two or more halogens, then the halogens may be same or        different.        [44] The compound according to the above [43], wherein Y^(9A) is        a methyl group or an ethyl group.

When R³ and G are R^(3-12A) and G^(12A) as defined below, respectively:

[45] A compound of the formula (12A):

wherein the symbols in the formula (12A) are defined as follows:

R^(3-12A) represents hydrogen, a C1-C6 alkyl group, or a (C1-C6alkoxy)C1-C6 alkyl group;

-   -   wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6 alkyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different, and

G^(12A) represents a phenyl group having a substituent selected fromGroup R^(4-12A) at 2-position;

-   -   wherein the phenyl group may optionally further have one or more        substituents selected from Group R^(4-12A-a), the substituents        may be same or different when the phenyl group has two or more        substituents;    -   the Group R^(4-12A) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkoxy group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        (C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl        group, a (C3-C6 cycloalkylamino)carbonyl group, a tri(C1-C6        alkyl)silyl group, a C6-C10 aryl group, and a 5- or 6-membered        heteroaryl group;    -   in the Group R^(4-12A), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group        4-12A, provided that when they have two or more substituents,        then the substituents may be same or different;    -   the Group 4-12A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the Group 4-12A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different;    -   the Group R^(4-12A-A) consists of halogen, a cyano group, a        nitro group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a (C1-C6 alkyl)carbonyl group, a (C3-C6        cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a        tri(C1-C6 alkyl)silyl group, a C6-C10 aryl group, and a 5- or        6-membered heteroaryl group;    -   in the Group R^(4-12A-a), the C1-C6 alkyl group, the C1-C6        alkoxy group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6        alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl        group, the C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group,        the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,        the (C3-C6 cycloalkyl)carbonyl group, and the (C1-C6        alkoxy)carbonyl group may be optionally substituted with one or        more halogens, provided that when they are substituted with two        or more halogens, then the halogens may be same or different;        and the C6-C10 aryl group and the 5- or 6-membered heteroaryl        group may optionally have one or more substituents selected from        Group 4-12A-a, provided that when they have two or more        substituents, then the substituents may be same or different;    -   the Group 4-12A-a consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkoxy)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group    -   in the Group 4-12A-a, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different.        [46] The compound according to the above [45], wherein G^(12a)        is a phenyl group having a substituent selected from Group        R^(4-12A-1) at 2-position wherein the phenyl group may        optionally further have one or more substituents selected from        Group R^(4-12A-a-1), the substituents may be same or different        when the phenyl group has two or more substituents;

the Group R^(4-12A-1) consists of halogen, a cyano group, a nitro group,a C1-C6 alkyl group, a C1-C6 alkoxy group, a C2-C6 alkynyl group, aC3-C6 cycloalkyl group, and a phenyl group;

in the Group R^(4-12A-1), the C1-C6 alkyl group, the C1-C6 alkoxy group,the C2-C6 alkynyl group, and the C3-C6 cycloalkyl group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; and the phenyl group may optionally have one or moresubstituents selected from Group 4-12A-1, provided that when it has twoor more substituents, then the substituents may be same or different;

the Group 4-12A-1 consists of halogen and a C1-C6 alkyl group;

in the Group 4-12A-1, the C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when it issubstituted with two or more halogens, then the halogens may be same ordifferent;

the Group R^(4-12A-a-1) consists of halogen, a cyano group, a nitrogroup, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C2-C6 alkynyl group,a C3-C6 cycloalkyl group, and a phenyl group;

in the Group R^(4-12A-a-1), the C1-C6 alkyl group, the C1-C6 alkoxygroup, the C2-C6 alkynyl group, and the C3-C6 cycloalkyl group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; and

in the Group R^(4-12A-a-1), the phenyl group may optionally have one ormore substituents selected from Group 4-12A-a-1, provided that when ithas two or more substituents, then the substituents may be same ordifferent;

the Group 4-12A-a-1 consists of halogen and a C1-C6 alkyl group;

in the Group 4-12A-a-1, the C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when it issubstituted with two or more halogens, then the halogens may be same ordifferent.

[47] The compound according to the above [45] or [46], wherein R^(3-12A)is a methyl group, and G^(12A) is a 2,4,6-triethylphenyl group or a2,6-diethyl-4-methylphenyl group.

[48] The method according to the above [7], wherein R¹ is hydrogen, amethyl group, an ethyl group, a n-butyl group or a phenyl group, R² is amethyl group, a 4-fluorophenyl group or a trifluoromethyl group, R³ is amethyl group or a benzyl group, R⁵ is a methyl group or a 4-methylphenylgroup, and G is a 2,4,6-triethylphenyl group, a2-ethyl-5-(4-chlorophenyl)phenyl group, a 1-methylindol-3-yl group or a2,6-diethyl-4-methylphenyl group.[49] The method according to above [13], wherein R¹ is hydrogen, amethyl group, an ethyl group, a n-butyl group or a phenyl group, R² is amethyl group or a 4-fluorophenyl group, R³ is a methyl group or a benzylgroup, R⁵ is a methyl group or a 4-methylphenyl group, and G is a2,4,6-triethylphenyl group, a 2-ethyl-5-(4-chlorophenyl)phenyl group, a1-methylindol-3-yl group or a 2,6-diethyl-4-methylphenyl group.[50] The method according to above [19], wherein R¹ is hydrogen, amethyl group, an ethyl group, a n-butyl group or a phenyl group, R² is amethyl group, or a trifluoromethyl group, R³ is a methyl group or abenzyl group, R⁵ is a methyl group or a 4-methylphenyl group, and G is a2,4,6-triethylphenyl group or a 2,6-diethyl-4-methylphenyl group.[51] A method for producing a compound of the formula (1B):

which comprises the steps of:reacting a compound of the formula (12B):

with a compound of the formula (20):

to obtain a compound of the formula (17):

reacting the compound of the formula (17) with a compound of the formula(18):L—R^(3D)  (18)to obtain a compound of the formula (19):

decomposing the compound of the formula (19) to obtain a compound of theformula (12C):

reacting the compound of the formula (12C) with a compound of theformula (7):

to obtain a compound of the formula (4B):

reacting the compound of the formula (4B) with a base to obtain acompound of the formula (2B):

reacting the compound of the formula (2B) with a compound of the formula(3):M(OR¹)_(v)  (3).[52] The method according to above [51], wherein

R¹ is hydrogen, a methyl group, an ethyl group, a n-butyl group, abenzyl group or a phenyl group,

R² is a methyl group, a trifluoromethyl group or a 4-fluorophenyl group,

R⁵ is a methyl group or a 4-methylphenyl group,

R^(3B) is a methyl group,

G^(B) is a 2,6-diethyl-4-methylphenyl group,

R¹⁰ is hydrogen or a methyl group,

R¹¹ is hydrogen, a methyl group, an ethyl group, an isopropyl group or aphenyl group, and

L is a methoxysulfonyloxy group.

[53] A method of for producing a compound of the formula (19):

which comprises reacting a compound of the formula (17):

with a compound of the formula (18):L—R^(3B)  (18)[54] The method according to above [53], wherein

R^(3B) is a C1-C6 alkyl group,

G^(B) is a phenyl group

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R⁴⁻¹⁰, provided that when it        has two or more substituents, then the substituents may be same        or different;    -   the Group R⁴⁻¹⁰ consists of a C1-C6 alkyl group and a phenyl        group;    -   in the Group R⁴⁻¹⁰, the phenyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R¹⁰ is hydrogen or a C1-C6 alkyl group; and

R¹¹ is hydrogen, a C1-C6 alkyl group or a phenyl group.

[55] The method according to above [53] wherein

R^(3B) is a methyl group,

G^(B) is a 2,6-diethyl-4-methylphenyl group,

R¹⁰ is hydrogen or methyl group,

R¹¹ is hydrogen, a methyl group, an ethyl group, an isopropyl group or aphenyl group, and

L is a methoxysulfonyloxy group.

[56] A method for producing a compound of the formula (12C):

which comprises decomposing a compound of the formula (19):

[57] The method according to above [56], wherein

R^(3B) is a C1-C6 alkyl group,

G^(B) is a phenyl group

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R⁴⁻¹¹, provided that when it        has two or more substituents, then the substituents may be same        or different;    -   the Group R⁴⁻¹¹ consists of a C1-C6 alkyl group and a phenyl        group;    -   in the Group R⁴⁻¹¹, the phenyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R¹⁰ is hydrogen or a C1-C6 alkyl group, and

R¹¹ is hydrogen, a C1-C6 alkyl group or a phenyl group.

[58] The method according to above [56] wherein

R^(3B) is a methyl group,

G^(B) is a 2,6-diethyl-4-methylphenyl group,

R¹⁰ is hydrogen or a methyl group, and

R¹¹ is hydrogen, a methyl group, an ethyl group, an isopropyl group or aphenyl group.

[59] A compound of the formula (17A):

wherein

G^(B-17A) represents a phenyl group;

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R^(4-17A), provided that when        it has two or more substituents, then the substituents may be        same or different;    -   the Group R^(4-17A) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4-17A), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl) carbonyl group, the        (C3-C6 cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl        group may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group        4-17A, provided that when they have two or more substituents,        then the substituents may be same or different;    -   the Group 4-17A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the Group 4-17A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and

R^(10-17A) and R^(11-17A) may be same or different, and each representshydrogen, a C1-C6 alkyl group, a C3-C6 cycloalkyl group or a phenylgroup, or R^(10-17A) and R^(11-17A) may be combined to form 5- or6-membered cyclic group with a carbon atom which is bonded withR^(10-17A) and R^(11-17A),

-   -   wherein the C1-C6 alkyl group and the C3-C6 cycloalkyl group may        be optionally substituted with one or more halogens, provided        that when they are substituted with two or more halogens, then        the halogens may be same or different; and the phenyl group may        optionally have one or more substituents selected from Group        10-17A, provided that when it has two or more substituents, then        the substituents may be same or different;    -   the Group 10-17A consists of halogen, a C1-C6 alkyl group and a        C1-C6 alkoxy group.        [60] The compound according to above [59], wherein

G^(B-17A) is a phenyl group

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R^(4-17A-1), provided that when        it has two or more substituents, then the substituents may be        same or different;    -   the Group R^(4-17A-1) consists of a C1-C6 alkyl group and a        phenyl group;    -   in the Group R^(4-17A-1), the phenyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R^(10-17A) is hydrogen or a C1-C6 alkyl group, and

R^(11-17A) is hydrogen, a C1-C6 alkyl group or a phenyl group.

[61] The compound according to above [59] wherein

G^(B-17A) is a 2,6-diethyl-4-methylphenyl group,

R^(10-17A) is hydrogen or a methyl group, and

R^(11-17A) is hydrogen, a methyl group, an ethyl group, an isopropylgroup or a phenyl group.

[62] A compound of the formula (19A):

wherein,

R^(3-19A) represents a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkylgroup, a (C1-C6 alkylthio)C1-C6 alkyl group, a C1-C6 alkylsulfonylgroup, a (C1-C6 alkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a(C1-C6 alkyl)aminocarbonyl group, a di(C1-C6 alkyl)aminocarbonyl group,a (C3-C6 cycloalkyl)aminocarbonyl group, a phenyl group, a benzyl group,or a phenylsulfonyl group;

-   -   wherein the C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl        group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the        C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkyl group,        the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,        and the (C1-C6 alkoxy)carbonyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different; and the phenyl group, the benzyl group,        and the phenylsulfonyl group may optionally have one or more        substituents selected from Group 3-19A, provided that when they        have two or more substituents, then the substituents may be same        or different,    -   the Group 3-19A consists of halogen, a C1-C6 alkyl group, a        C1-C6 alkoxy group, and a (C1-C6 alkoxy)C1-C6 alkyl group;    -   in the Group 3-19A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, and the (C1-C6 alkoxy)C1-C6 alkyl group may be optionally        substituted with one or more halogens, provided that when they        are substituted with two or more halogens, then the halogens may        be same or different;

G^(B-19A) represents a phenyl group;

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R^(4-19A), provided that when        it has two or more substituents, then the substituents may be        same or different;    -   the Group R^(4-19A) consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a        C6-C10 aryl group, and a 5- or 6-membered heteroaryl group;    -   in the Group R^(4-19A), the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and the        C6-C10 aryl group and the 5- or 6-membered heteroaryl group may        optionally have one or more substituents selected from Group        4-19A, provided that when they have two or more substituents,        then the substituents may be same or different;    -   the Group 4-19A consists of halogen, a cyano group, a nitro        group, a formyl group, a C1-C6 alkyl group, a C1-C6 alkoxy        group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,        a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6        alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6        alkylsulfonyl group, a C1-C6 alkylamino group, a di(C1-C6        alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6        alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a        (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)Carbonyl        group, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6        cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silyl        group;    -   in the Group 4-19A, the C1-C6 alkyl group, the C1-C6 alkoxy        group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl        group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the        C1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6        alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6        cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group        may be optionally substituted with one or more halogens,        provided that when they are substituted with two or more        halogens, then the halogens may be same or different; and

R^(10-19A) and R^(11-19A) may be same or different, and each representshydrogen, a C1-C6 alkyl group, a C3-C6 cycloalkyl group or a phenylgroup, or R^(10-19A) and R^(11-19A) may be combined to form 5- or6-membered cyclic group with a carbon atom which is bonded withR^(10-17A) and R^(11-17A),

-   -   wherein the C1-C6 alkyl group and the C3-C6 cycloalkyl group may        be optionally substituted with one or more halogens, provided        that when they are substituted with two or more halogens, then        the halogens may be same or different; and the phenyl group may        optionally have one or more substituents selected from Group        10-19A, provided that when it has two or more substituents, then        the substituents may be same or different;    -   the Group 10-19A consists of halogen, a C1-C6 alkyl group and a        C1-C6 alkoxy group.        [63] The compound according to above [62], wherein

G^(B-19A) is a phenyl group

-   -   wherein the phenyl group may optionally have one or more        substituents selected from Group R^(4-19A-1), provided that when        it has two or more substituents, then the substituents may be        same or different;    -   the Group R^(4-19A-1) consists of a C1-C6 alkyl group and a        phenyl group;    -   in the Group R^(4-19A-1), the phenyl group may be optionally        substituted with one or more halogens, provided that when it is        substituted with two or more halogens, then the halogens may be        same or different;

R^(3-19A) is a C1-C6 alkyl group,

R^(10-19A) is hydrogen or a C1-C6 alkyl group, and

R^(11-19A) is hydrogen, a C1-C6 alkyl group or a phenyl group.

[64] The compound according to above [62] wherein

G^(B-19A) is a 2,6-diethyl-4-methylphenyl group,

R^(8-19A) is a C1-C6 alkyl group,

R^(10-19A) is hydrogen or a methyl group, and

R^(11-19A) is hydrogen, a methyl group, and ethyl group, an isopropylgroup or a phenyl group.

DESCRIPTIONS OF EMBODIMENTS

Examples of each of the substituents described herein are shown below:

halogen: fluorine, chlorine, bromine and iodine;

C1-C6 alkyl group optionally substituted with one or more halogens: amethyl group, an ethyl group, a n-propyl group, an isopropyl group, abutyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an-pentyl group, a n-hexyl group, a trifluoromethyl group, and a2,2,2-trifluoroethyl group;

C1-C6 alkoxy group optionally substituted with one or more halogens: amethoxy group, a trifluoromethoxy group, an ethoxy group, a2,2,2-trifluoroethoxy group, a propyloxy group, an isopropyloxy group, abutoxy group, an isobutyloxy group, a sec-butoxy group, a tert-butoxygroup, a pentyloxy group, and a hexyloxy group;

(C1-C6 alkoxy)C1-C6 alkyl group optionally substituted with one or morehalogens: a methoxymethyl group, a 2-methoxyethyl group, a 2-ethoxyethylgroup, a 2-isopropyloxyethyl group, and a 2-trifluoromethoxyethyl group;

C2-C6 alkenyl group optionally substituted with one or more halogens: aethenyl group, a 2-propenyl group, a 3-chloro-2-propenyl group, a2-chloro-2-propenyl group, a 3,3-dichloro-2-propenyl group, a 2-butenylgroup, a 3-butenyl group, a 2-methyl-2-propenyl group, a3-methyl-2-butenyl group, a 2-pentenyl group, and a 1-hexenyl group;

C2-C6 alkynyl group optionally substituted with one or more halogens: aethynyl group, a 2-propynyl group, a 3-chloro-2-propynyl group, a3-bromo-2-propynyl group, a 2-butynyl group, a 3-butynyl group, a2-pentynyl group, and a 2-hexynyl group;

C3-C6 cycloalkyl group optionally substituted with one or more halogens:a cyclopropyl group, a 2-chlorocyclopropyl group, a 2-bromocyclopropylgroup, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group;

C1-C6 alkylthio group optionally substituted with one or more halogens:a methylthio group, a trifluoromethylthio group, and ethylthio group, apropylthio group, a butylthio group, a pentylthio group, and a hexylthiogroup;

C1-C6 alkylsulfinyl group optionally substituted with one or morehalogens: a methylsulfinyl group, a trifluoromethylsulfinyl group, anethylsulfinyl group, a propylsulfinyl group, a pentylsulfinyl group, anda hexylsulfinyl group;

C1-C6 alkylsulfonyl group optionally substituted with one or morehalogens: a methylsulfonyl group, a trifluoromethylsulfonyl group, andan ethylsulfonyl group, a propylsulfonyl group, a pentylsulfonyl group,and a hexylsulfonyl group;

(C1-C6 alkylthio)C1-C6 alkyl group optionally substituted with one ormore halogens: a methylthiomethyl group, a methylthioethyl group, atrifluoromethylthiomethyl group, and an ethylthiomethyl group;

(C1-C6 alkylsulfinyl)C1-C6 alkyl group optionally substituted with oneor more halogens: a methylsulfinylmethyl group, a methylsulfinylethylgroup, a trifluoromethylsulfonylmethyl group, and an ethylsulfinylmethylgroup;

(C1-C6 alkylsulfonyl)C1-C6 alkyl group optionally substituted with oneor more halogens: a methylsulfonylmethyl group, a methylsulfonylethylgroup, a trifluoromethylsulfonylmethyl group, and an ethylsulfonylmethylgroup;

C1-C6 alkylamino group: a methylamino group, an ethylamino group, apropylamino group, an isopropylamino group, a butylamino group, anisobutylamino group, a sec-butylamino group, a tert-butylamino group, apentylamino group, and a hexylamino group;

di(C1-C6 alkyl)amino group: a dimethylamino group, a diethylamino group,an ethylmethylamino group, a dipropylamino group, a diisopropylaminogroup, a dibutylamino group, and a methylpropylamino group;

C3-C6 cycloalkylamino group: a cyclopropylamino group, a cyclobutylaminogroup, a cyclopentylamino group, and a cyclohexylamino group;

(C1-C6 alkyl)carbonyl group optionally substituted with one or morehalogens: an acetyl group, a trifluoroacetyl group, a propionyl group, apentafluoropropionyl group, an isobutyryl group, and a trimethylacetylgroup;

(C3-C6 cycloalkyl)carbonyl group optionally substituted with one or morehalogens: a cyclopropylcarbonyl group, a 2-chlorocyclopropylcarbonylgroup, a 2-bromocyclopropylcarbonyl group, a cyclobutylcarbonyl group, acyclopentylcarbonyl group, and a cyclohexylcarbonyl group;

(C1-C6 alkoxy)carbonyl group optionally substituted with one or morehalogens: a methoxycarbonyl group, an ethoxycarbonyl group, a2,2,2-trifluoroethoxycarbonyl group, a propyloxycarbonyl group, anisopropyloxycarbonyl group, and a butoxycarbonyl group;

(C1-C6 alkylamino)carbonyl group: a methylaminocarbonyl group, anethylaminocarbonyl group, a propylaminocarbonyl group, and anisopropylaminocarbonyl group;

di(C1-C6 alkyl)aminocarbonyl group: a dimethylaminocarbonyl group, adiethylaminocarbonyl group, an ethylmethylaminocarbonyl group, adipropylaminocarbonyl group, a diisopropylaminocarbonyl group, adibutylaminocarbonyl group, and a methylpropylaminocarbonyl group;

(C3-C6 cycloalkylamino)carbonyl group: a cyclopropylaminocarbonyl group,a cyclobutylaminocarbonyl group, a cyclopentylaminocarbonyl group, and acyclohexylaminocarbonyl group;

tri(C1-C6 alkyl)silyl group: a trimethylsilyl group, a triethylsilylgroup, and a diethylisopropylsilyl group;

C6-C10 aryl group optionally having one or more substituents: a phenylgroup, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenylgroup, a 2,3-dimethylphenyl group, a 2,4-dimethylphenyl group, a3,4-dimethylphenyl group, a 2,5-dimethylphenyl group, a2,6-dimethylphenyl group, a 3,5-dimethylphenyl group, a2,3,4-trimethylphenyl group, a 2,3,5-trimethylphenyl group, a2,3,6-trimethylphenyl group, a 2,4,5-trimethylphenyl group, a2,4,6-trimethylphenyl group, a 3,4,5-trimethylphenyl group, a2-ethylphenyl group, a 3-ethylphenyl group, a 4-ethylphenyl group, a2,3-diethylphenyl group, a 2,4-diethylphenyl group, a 3,4-diethylphenylgroup, a 2,5-diethylphenyl group, a 2,6-diethylphenyl group, a3,5-diethylphenyl group, a 2,3,4-triethylphenyl group, a2,3,5-triethylphenyl group, a 2,3,6-triethylphenyl group, a2,4,5-triethylphenyl group, a 2,4,6-triethylphenyl group, a3,4,5-triethylphenyl group, a 2-fluorophenyl group, a 3-fluorophenylgroup, a 4-fluorophenyl group, a 2,3-difluorophenyl group, a2,4-difluorophenyl group, a 3,4-difluorophenyl group, a2,5-difluorophenyl group, a 2,6-difluorophenyl group, a3,5-difluorophenyl group, a 2,3,4-trifluorophenyl group, a2,3,5-trifluorophenyl group, a 2,3,6-trifluorophenyl group, a2,4,5-trifluorophenyl group, a 2,4,6-trifluorophenyl group, a3,4,5-trifluorophenyl group, a 2-chlorophenyl group, a 3-chlorophenylgroup, a 4-chlorophenyl group, a 2,3-dichlorophenyl group, a2,4-dichlorophenyl group, a 3,4-dichlorophenyl group, a2,5-dichlorophenyl group, a 2,6-dichlorophenyl group, a3,5-dichlorophenyl group, a 2,3,4-trichlorophenyl group, a2,3,5-trichlorophenyl group, a 2,3,6-trichlorophenyl group, a2,4,5-trichlorophenyl group, a 2,4,6-trichlorophenyl group, a3,4,5-trichlorophenyl group, a 2-bromophenyl group, a 3-bromophenylgroup, a 4-bromophenyl group, a 2,3-dibromophenyl group, a2,4-dibromophenyl group, a 3,4-dibromophenyl group, a 2,5-dibromophenylgroup, a 2,6-dibromophenyl group, a 3,5-dibromophenyl group, a2,3,4-tribromophenyl group, a 2,3,5-tribromophenyl group, a2,3,6-tribromophenyl group, a 2,4,5-tribromophenyl group, a2,4,6-tribromophenyl group, a 3,4,5-tribromophenyl group, a 2-iodophenylgroup, a 3-iodophenyl group, a 4-iodophenyl group, a 2,3-diiodophenylgroup, a 2,4-diiodophenyl group, a 3,4-diiodophenyl group, a2,5-diiodophenyl group, a 2,6-diiodophenyl group, a 3,5-diiodophenylgroup a 2,3,4-triiodophenyl group, a 2,3,5-triiodophenyl group, a2,3,6-triiodophenyl group, a 2,4,5-triiodophenyl group, a2,4,6-triiodophenyl group, a 3,4,5-triiodophenyl group, a2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group,a 2,3-dimethoxyphenyl group, a 2,4-dimethoxyphenyl group, a3,4-dimethoxyphenyl group, a 2,5-dimethoxyphenyl group, a2,6-dimethoxyphenyl group, a 3,5-dimethoxyphenyl group, a2,3,4-trimethoxyphenyl group, a 2,3,5-trimethoxyphenyl group, a2,3,6-trimethoxyphenyl group, a 2,4,5-trimethoxyphenyl group, a2,4,6-trimethoxyphenyl group, a 3,4,5-trimethoxyphenyl group, a2-trifluoromethylphenyl group, a 3-trifluoromethylphenyl group, a4-trifluoromethylphenyl group, a 2,3-bis(trifluoromethyl)phenyl group,2,4-bis(trifluoromethyl)phenyl group, a 3,4-bis(trifluoromethyl)phenylgroup, a 2,5-bis(trifluoromethyl)phenyl group, a2,6-bis(trifluoromethyl)-phenyl group, a 3,5-bis(trifluoromethyl)phenylgroup, a 2,3,4-tris(trifluoromethyl)phenyl group, a2,3,5-tris(trifluoromethyl)phenyl group, a2,3,6-tris(trifluoromethyl)phenyl group, a2,4,5-tris(trifluoromethyl)phenyl group, a2,4,6-tris(trifluoromethyl)phenyl group, a3,4,5-tris(trifluoromethyl)phenyl group, a 2-ethyl-3-methylphenyl group,a 3-ethyl-2-methylphenyl group, a 2-ethyl-4-methylphenyl group, a4-ethyl-2-methylphenyl group, a 3-ethyl-4-methylphenyl group, a4-ethyl-3-methylphenyl group, a 5-ethyl-2-methylphenyl group, a2-ethyl-5-methylphenyl group, a 2-ethyl-6-methylphenyl group, a3-ethyl-5-methylphenyl group, a 2,3-diethyl-4-methylphenyl group, a2,4-diethyl-3-methylphenyl group, a 3,4-diethyl-2-methylphenyl group, a4-ethyl-2,3-dimethylphenyl group, a 3-ethyl-2,4-dimethylphenyl group, a2-ethyl-3,4-dimethylphenyl group, a 3,5-diethyl-2-methylphenyl group, a2,5-diethyl-3-methylphenyl group, a 2,3-diethyl-5-methylphenyl group, a2-ethyl-3,5-dimethylphenyl group, a 3-ethyl-2,5-dimethylphenyl group, a5-ethyl-2,3-dimethylphenyl group, a 2,3-diethyl-6-methylphenyl group, a2,6-diethyl-3-methylphenyl group, a 3,6-diethyl-2-methylphenyl group, a6-ethyl-2,3-dimethylphenyl group, a 3-ethyl-2,6-dimethylphenyl group, a2-ethyl-3,6-dimethylphenyl group, a 2,4-diethyl-5-methylphenyl group, a2,5-diethyl-4-methylphenyl group, a 4,5-diethyl-2-methylphenyl group, a5-ethyl-2,4-dimethylphenyl group, a 4-ethyl-2,5-dimethylphenyl group, a2-ethyl-4,5-dimethylphenyl group, a 2,4-diethyl-6-methylphenyl group, a2,6-diethyl-4-methylphenyl group, a 6-ethyl-2,4-dimethylphenyl group, a4-ethyl-2,6-dimethylphenyl group, a 3,4-diethyl-5-methylphenyl group, a3,5-diethyl-4-methylphenyl group, a 5-ethyl-3,4-dimethylphenyl group, a4-ethyl-3,5-dimethylphenyl group, a 2-fluoro-3-methylphenyl group, a3-fluoro-2-methylphenyl group, a 2-fluoro-4-methylphenyl group, a4-fluoro-2-methylphenyl group, a 3-fluoro-4-methylphenyl group, a4-fluoro-3-methylphenyl group, a 5-fluoro-2-methylphenyl group, a2-fluoro-5-methylphenyl group, a 2-fluoro-6-methylphenyl group, a3-fluoro-5-methylphenyl group, a 2,3-difluoro-4-methylphenyl group, a2,4-difluoro-3-methylphenyl group, a 3,4-difluoro-2-methylphenyl group,a 4-fluoro-2,3-dimethylphenyl group, a 3-fluoro-2,4-dimethylphenylgroup, a 2-fluoro-3,4-dimethylphenyl group, a3,5-difluoro-2-methylphenyl group, a 2,5-difluoro-3-methylphenyl group,a 2,3-difluoro-5-methylphenyl group, a 2-fluoro-3,5-dimethylphenylgroup, a 3-fluoro-2,5-dimethylphenyl group, a5-fluoro-2,3-dimethylphenyl group, a 2,3-difluoro-6-methylphenyl group,a 2,6-difluoro-3-methylphenyl group, a 3,6-difluoro-2-methylphenylgroup, a 6-fluoro-2,3-dimethylphenyl group, a3-fluoro-2,6-dimethylphenyl group, a 2-fluoro-3,6-dimethylphenyl group,a 2,4-difluoro-5-methylphenyl group, a 2,5-difluoro-4-methylphenylgroup, a 4,5-difluoro-2-methylphenyl group, a5-fluoro-2,4-dimethylphenyl group, a 4-fluoro-2,5-dimethylphenyl group,a 2-fluoro-4,5-dimethylphenyl group, a 2,4-difluoro-6-methylphenylgroup, a 2,6-difluoro-4-methylphenyl group, a6-fluoro-2,4-dimethylphenyl group, a 4-fluoro-2,6-dimethylphenyl group,a 3,4-difluoro-5-methylphenyl group, a 3,5-difluoro-4-methylphenylgroup, a 5-fluoro-3,4-dimethylphenyl group, a4-fluoro-3,5-dimethylphenyl group, a 2-chloro-3-methylphenyl group, a3-chloro-2-methylphenyl group, a 2-chloro-4-methylphenyl group, a4-chloro-2-methylphenyl group, a 3-chloro-4-methylphenyl group, a4-chloro-3-methylphenyl group, a 5-chloro-2-methylphenyl group, a2-chloro-5-methylphenyl group, a 2-chloro-6-methylphenyl group, a3-chloro-5-methylphenyl group, a 2,3-dichloro-4-methylphenyl group, a2,4-dichloro-3-methylphenyl group, a 3,4-dichloro-2-methylphenyl group,a 4-chloro-2,3-dimethylphenyl group, a 3-chloro-2,4-dimethylphenylgroup, a 2-chloro-3,4-dimethyl-phenyl group, a3,5-dichloro-2-methylphenyl group, a 2,5-dichloro-3-methylphenyl group,a 2,3-dichloro-5-methylphenyl group, a 2-chloro-3,5-dimethylphenylgroup, a 3-chloro-2,5-dimethylphenyl group, a5-chloro-2,3-dimethylphenyl group, a 2,3-dichloro-6-methylphenyl group,a 2,6-dichloro-3-methylphenyl group, a 3,6-dichloro-2-methylphenylgroup, a 6-chloro-2,3-dimethylphenyl group, a3-chloro-2,6-dimethylphenyl group, a 2-chloro-3,6-dimethylphenyl group,a 2,4-dichloro-5-methylphenyl group, a 2,5-dichloro-4-methylphenylgroup, a 4,5-dichloro-2-methylphenyl group, a5-chloro-2,4-dimethylphenyl group, a 4-chloro-2,5-dimethylphenyl group,a 2-chloro-4,5-dimethylphenyl group, a 2,4-dichloro-6-methylphenylgroup, a 2,6-dichloro-4-methylphenyl group, a6-chloro-2,4-dimethylphenyl group, a 4-chloro-2,6-dimethylphenyl group,a 3,4-dichloro-5-methylphenyl group, a 3,5-dichloro-4-methylphenylgroup, a 5-chloro-3,4-dimethylphenyl group, a4-chloro-3,5-dimethylphenyl group, a 2-bromo-3-methylphenyl group, a3-bromo-2-methylphenyl group, a 2-bromo-4-methylphenyl group, a4-bromo-2-methylphenyl group, a 3-bromo-4-methylphenyl group, a4-bromo-3-methylphenyl group, a 5-bromo-2-methylphenyl group, a2-bromo-5-methylphenyl group, a 2-bromo-6-methylphenyl group, a3-bromo-5-methylphenyl group, a 2,3-dibromo-4-methylphenyl group, a2,4-dibromo-3-methylphenyl group, a 3,4-dibromo-2-methylphenyl group, a4-bromo-2,3-dimethylphenyl group, a 3-bromo-2,4-dimethylphenyl group, a2-bromo-3,4-dimethylphenyl group, a 3,5-dibromo-2-methylphenyl group, a2,5-dibromo-3-methylphenyl group, a 2,3-dibromo-5-methylphenyl group, a2-bromo-3,5-dimethylphenyl group, a 3-bromo-2,5-dimethylphenyl group, a5-bromo-2,3-dimethylphenyl group, a 2,3-dibromo-6-methylphenyl group, a2,6-dibromo-3-methylphenyl group, a 3,6-dibromo-2-methylphenyl group, a6-bromo-2,3-dimethylphenyl group, a 3-bromo-2,6-dimethylphenyl group, a2-bromo-3,6-dimethylphenyl group, a 2,4-dibromo-5-methylphenyl group, a2,5-dibromo-4-methylphenyl group, a 4,5-dibromo-2-methylphenyl group, a5-bromo-2,4-dimethylphenyl group, a 4-bromo-2,5-dimethylphenyl group, a2-bromo-4,5-dimethylphenyl group, a 2,4-dibromo-6-methylphenyl group, a2,6-dibromo-4-methylphenyl group, a 6-bromo-2,4-dimethylphenyl group, a4-bromo-2,6-dimethylphenyl group, a 3,4-dibromo-5-methylphenyl group, a3,5-dibromo-4-methylphenyl group, a 5-bromo-3,4-dimethylphenyl group, a4-bromo-3,5-dimethylphenyl group, a 2-ethyl-3-fluorophenyl group, a3-ethyl-2-fluorophenyl group, a 2-ethyl-4-fluorophenyl group, a4-ethyl-2-fluorophenyl group, a 3-ethyl-4-fluorophenyl group, a4-ethyl-3-fluorophenyl group, a 5-ethyl-2-fluorophenyl group, a2-ethyl-5-fluorophenyl group, a 2-ethyl-6-fluorophenyl group, a3-ethyl-5-fluorophenyl group, a 2,3-diethyl-4-fluorophenyl group, a2,4-diethyl-3-fluorophenyl group, a 3,4-diethyl-2-fluorophenyl group, a4-ethyl-2,3-difluorophenyl group, a 3-ethyl-2,4-difluorophenyl group, a2-ethyl-3,4-difluorophenyl group, a 3,5-diethyl-2-fluorophenyl group, a2,5-diethyl-3-fluorophenyl group, a 2,3-diethyl-5-fluorophenyl group, a2-ethyl-3,5-difluorophenyl group, a 3-ethyl-2,5-difluorophenyl group, a5-ethyl-2,3-difluorophenyl group, a 2,3-diethyl-6-fluorophenyl group, a2,6-diethyl-3-fluorophenyl group, a 3,6-diethyl-2-fluorophenyl group, a6-ethyl-2,3-difluorophenyl group, a 3-ethyl-2,6-difluorophenyl group, a2-ethyl-3,6-difluorophenyl group, a 2,4-diethyl-5-fluorophenyl group, a2,5-diethyl-4-fluorophenyl group, a 4,5-diethyl-2-fluorophenyl group, a5-ethyl-2,4-difluorophenyl group, a 4-ethyl-2,5-difluorophenyl group, a2-ethyl-4,5-difluorophenyl group, a 2,4-diethyl-6-fluorophenyl group, a2,6-diethyl-4-fluorophenyl group, a 6-ethyl-2,4-difluorophenyl group, a4-ethyl-2,6-difluorophenyl group, a 3,4-diethyl-5-fluorophenyl group, a3,5-diethyl-4-fluorophenyl group, a 5-ethyl-3,4-difluorophenyl group, a4-ethyl-3,5-difluorophenyl group, a 2-chloro-3-ethylphenyl group, a3-chloro-2-ethylphenyl group, a 2-chloro-4-ethylphenyl group, a4-chloro-2-ethylphenyl group, a 3-chloro-4-ethylphenyl group, a4-chloro-3-ethylphenyl group, a 5-chloro-2-ethylphenyl group, a2-chloro-5-ethylphenyl group, a 2-chloro-6-ethylphenyl group, a3-chloro-5-ethylphenyl group, a 2,3-dichloro-4-ethylphenyl group, a2,4-dichloro-3-ethylphenyl group, a 3,4-dichloro-2-ethylphenyl group, a4-chloro-2,3-diethylphenyl group, a 3-chloro-2,4-diethylphenyl group, a2-chloro-3,4-diethylphenyl group, a 3,5-dichloro-2-ethylphenyl group, a2,5-dichloro-3-ethylphenyl group, a 2,3-dichloro-5-ethylphenyl group, a2-chloro-3,5-diethylphenyl group, a 3-chloro-2,5-diethylphenyl group, a5-chloro-2,3-diethylphenyl group, a 2,3-dichloro-6-ethylphenyl group, a2,6-dichloro-3-ethylphenyl group, a 3,6-dichloro-2-ethylphenyl group, a6-chloro-2,3-diethylphenyl group, a 3-chloro-2,6-diethylphenyl group, a2-chloro-3,6-diethylphenyl group, a 2,4-dichloro-5-ethylphenyl group, a2,5-dichloro-4-ethylphenyl group, a 4,5-dichloro-2-ethylphenyl group, a5-chloro-2,4-diethylphenyl group, a 4-chloro-2,5-diethylphenyl group, a2-chloro-4,5-diethylphenyl group, a 2,4-dichloro-6-ethylphenyl group, a2,6-dichloro-4-ethylphenyl group, a 6-chloro-2,4-diethylphenyl group, a4-chloro-2,6-diethylphenyl group, a 3,4-dichloro-5-ethylphenyl group, a3,5-dichloro-4-ethylphenyl group, a 5-chloro-3,4-diethylphenyl group, a4-chloro-3,5-diethylphenyl group, a 2-bromo-3-ethylphenyl group, a3-bromo-2-ethylphenyl group, a 2-bromo-4-ethylphenyl group, a4-bromo-2-ethylphenyl group, a 3-bromo-4-ethylphenyl group, a4-bromo-3-ethylphenyl group, a 5-bromo-2-ethylphenyl group, a2-bromo-5-ethylphenyl group, a 2-bromo-6-ethylphenyl group, a3-bromo-5-ethylphenyl group, a 2,3-dibromo-4-ethylphenyl group, a2,4-dibromo-3-ethylphenyl group, a 3,4-dibromo-2-ethylphenyl group, a4-bromo-2,3-diethylphenyl group, a 3-bromo-2,4-diethylphenyl group, a2-bromo-3,4-diethylphenyl group, a 3,5-dibromo-2-ethylphenyl group, a2,5-dibromo-3-ethylphenyl group, a 2,3-dibromo-5-ethylphenyl group, a2-bromo-3,5-diethylphenyl group, a 3-bromo-2,5-diethylphenyl group, a5-bromo-2,3-diethylphenyl group, a 2,3-dibromo-6-ethylphenyl group, a2,6-dibromo-3-ethylphenyl group, a 3,6-dibromo-2-ethylphenyl group, a6-bromo-2,3-diethylphenyl group, a 3-bromo-2,6-diethylphenyl group, a2-bromo-3,6-diethylphenyl group, a 2,4-dibromo-5-ethylphenyl group, a2,5-dibromo-4-ethylphenyl group, a 4,5-dibromo-2-ethylphenyl group, a5-bromo-2,4-diethylphenyl group, a 4-bromo-2,5-diethylphenyl group, a2-bromo-4,5-diethylphenyl group, a 2,4-dibromo-6-ethylphenyl group, a2,6-dibromo-4-ethylphenyl group, a 6-bromo-2,4-diethylphenyl group, a4-bromo-2,6-diethylphenyl group, a 3,4-dibromo-5-ethylphenyl group, a3,5-dibromo-4-ethylphenyl group, a 5-bromo-3,4-diethylphenyl group, a4-bromo-3,5-diethylphenyl group, a 2-chloro-3-fluorophenyl group, a3-chloro-2-fluorophenyl group, a 2-chloro-4-fluorophenyl group, a4-chloro-2-fluorophenyl group, a 3-chloro-4-fluorophenyl group, a4-chloro-3-fluorophenyl group, a 5-chloro-2-fluorophenyl group, a2-chloro-5-fluorophenyl group, a 2-chloro-6-fluorophenyl group, a3-chloro-5-fluorophenyl group, a 2,3-dichloro-4-fluorophenyl group, a2,4-dichloro-3-fluorophenyl group, a 3,4-dichloro-2-fluorophenyl group,a 4-chloro-2,3-difluorophenyl group, a 3-chloro-2,4-difluorophenylgroup, a 2-chloro-3,4-difluorophenyl group, a3,5-dichloro-2-fluorophenyl group, a 2,5-dichloro-3-fluorophenyl group,a 2,3-dichloro-5-fluorophenyl group, a 2-chloro-3,5-difluorophenylgroup, a 3-chloro-2,5-difluorophenyl group, a5-chloro-2,3-difluorophenyl group, a 2,3-dichloro-6-fluorophenyl group,a 2,6-dichloro-3-fluorophenyl group, a 3,6-dichloro-2-fluorophenylgroup, a 6-chloro-2,3-difluorophenyl group, a3-chloro-2,6-difluorophenyl group, a 2-chloro-3,6-difluorophenyl group,a 2,4-dichloro-5-fluorophenyl group, a 2,5-dichloro-4-fluorophenylgroup, a 4,5-dichloro-2-fluorophenyl group, a5-chloro-2,4-difluorophenyl group, a 4-chloro-2,5-difluorophenyl group,a 2-chloro-4,5-difluorophenyl group, a 2,4-dichloro-6-fluorophenylgroup, a 2,6-dichloro-4-fluorophenyl group, a6-chloro-2,4-difluorophenyl group, a 4-chloro-2,6-difluorophenyl group,a 3,4-dichloro-5-fluorophenyl group, a 3,5-dichloro-4-fluorophenylgroup, a 5-chloro-3,4-difluorophenyl group, a4-chloro-3,5-difluorophenyl group, a 2-bromo-3-chlorophenyl group, a3-bromo-2-chlorophenyl group, a 2-bromo-4-chlorophenyl group, a4-bromo-2-chlorophenyl group, a 3-bromo-4-chlorophenyl group, a4-bromo-3-chlorophenyl group, a 5-bromo-2-chlorophenyl group, a2-bromo-5-chlorophenyl group, a 2-bromo-6-chlorophenyl group, a3-bromo-5-chlorophenyl group, a 2,3-dibromo-4-chlorophenyl group, a2,4-dibromo-3-chlorophenyl group, a 3,4-dibromo-2-chlorophenyl group, a4-bromo-2,3-dichlorophenyl group, a 3-bromo-2,4-dichlorophenyl group, a2-bromo-3,4-dichlorophenyl group, a 3,5-dibromo-2-chlorophenyl group, a2,5-dibromo-3-chlorophenyl group, a 2,3-dibromo-5-chlorophenyl group, a2-bromo-3,5-dichlorophenyl group, a 3-bromo-2,5-dichlorophenyl group, a5-bromo-2,3-dichlorophenyl group, a 2,3-dibromo-6-chlorophenyl group, a2,6-dibromo-3-chlorophenyl group, a 3,6-dibromo-2-chlorophenyl group, a6-bromo-2,3-dichlorophenyl group, a 3-bromo-2,6-dichlorophenyl group, a2-bromo-3,6-dichlorophenyl group, a 2,4-dibromo-5-chlorophenyl group, a2,5-dibromo-4-chlorophenyl group, a 4,5-dibromo-2-chlorophenyl group, a5-bromo-2,4-dichlorophenyl group, a 4-bromo-2,5-dichlorophenyl group, a2-bromo-4,5-dichlorophenyl group, a 2,4-dibromo-6-chlorophenyl group, a2,6-dibromo-4-chlorophenyl group, a 6-bromo-2,4-dichlorophenyl group, a4-bromo-2,6-dichlorophenyl group, a 3,4-dibromo-5-chlorophenyl group, a3,5-dibromo-4-chlorophenyl group, a 5-bromo-3,4-dichlorophenyl group, a4-bromo-3,5-dichlorophenyl group, a 2-cyano-3-methylphenyl group, a3-cyano-2-methylphenyl group, a 2-cyano-4-methylphenyl group, a4-cyano-2-methylphenyl group, a 3-cyano-4-methylphenyl group, a4-cyano-3-methylphenyl group, a 5-cyano-2-methylphenyl group, a2-cyano-5-methylphenyl group, a 2-cyano-6-methylphenyl group, a3-cyano-5-methylphenyl group, a 4-cyano-2,3-dimethylphenyl group, a3-cyano-2,4-dimethylphenyl group, a 2-cyano-3,4-dimethyl-phenyl group, a2-cyano-3,5-dimethylphenyl group, a 3-cyano-2,5-dimethylphenyl group, a5-cyano-2,3-dimethylphenyl group, a 6-cyano-2,3-dimethylphenyl group, a3-cyano-2,6-dimethylphenyl group, a 2-cyano-3,6-dimethylphenyl group, a5-cyano-2,4-dimethylphenyl group, a 4-cyano-2,5-dimethylphenyl group, a2-cyano-4,5-dimethylphenyl group, a 6-cyano-2,4-dimethylphenyl group, a4-cyano-2,6-dimethylphenyl group, a 5-cyano-3,4-dimethylphenyl group, a4-cyano-3,5-dimethylphenyl group, a 2-methyl-3-trifluoromethylphenylgroup, a 3-methyl-2-trifluoromethylphenyl group, a2-methyl-4-trifluoromethylphenyl group, a4-methyl-2-trifluoromethylphenyl group, a3-methyl-4-trifluoromethylphenyl group, a4-methyl-3-trifluoromethylphenyl group, a5-methyl-2-trifluoromethylphenyl group, a2-methyl-5-trifluoromethylphenyl group, a2-methyl-6-trifluoromethylphenyl group, a3-methyl-5-trifluoromethylphenyl group, a2,3-dimethyl-4-trifluoromethylphenyl group, a2,4-dimethyl-3-trifluoromethylphenyl group, a3,4-dimethyl-2-trifluoromethylphenyl group, a3,5-dimethyl-2-trifluoromethylphenyl group, a2,5-dimethyl-3-trifluoromethylphenyl group, a2,3-dimethyl-5-trifluoromethylphenyl group, a2,3-dimethyl-6-trifluoromethylphenyl group, a2,6-dimethyl-3-trifluoromethylphenyl group, a3,6-dimethyl-2-trifluoromethylphenyl group, a2,4-dimethyl-5-trifluoromethylphenyl group, a2,5-dimethyl-4-trifluoromethylphenyl group, a4,5-dimethyl-2-trifluoromethylphenyl group, a2,4-dimethyl-6-trifluoromethylphenyl group, a2,6-dimethyl-4-trifluoromethylphenyl group, a3,4-dimethyl-5-trifluoromethylphenyl group, a3,5-dimethyl-4-trifluoromethylphenyl group, a2-cyclopropyl-3-methylphenyl group, a 3-cyclopropyl-2-methylphenylgroup, a 2-cyclopropyl-4-methylphenyl group, a4-cyclopropyl-2-methylphenyl group, a 3-cyclopropyl-4-methylphenylgroup, a 4-cyclopropyl-3-methylphenyl group, a5-cyclopropyl-2-methylphenyl group, a 2-cyclopropyl-5-methylphenylgroup, a 2-cyclopropyl-6-methylphenyl group, a3-cyclopropyl-5-methylphenyl group, a 4-cyclopropyl-2,3-dimethylphenylgroup, a 3-cyclopropyl-2,4-dimethylphenyl group, a2-cyclopropyl-3,4-dimethylphenyl group, a2-cyclopropyl-3,5-dimethylphenyl group, a3-cyclopropyl-2,5-dimethylphenyl group, a5-cyclopropyl-2,3-dimethylphenyl group, a6-cyclopropyl-2,3-dimethylphenyl group, a3-cyclopropyl-2,6-dimethylphenyl group, a2-cyclopropyl-3,6-dimethylphenyl group, a5-cyclopropyl-2,4-dimethylphenyl group, a4-cyclopropyl-2,5-dimethylphenyl group, a2-cyclopropyl-4,5-dimethylphenyl group, a6-cyclopropyl-2,4-dimethylphenyl group, a4-cyclopropyl-2,6-dimethylphenyl group, a5-cyclopropyl-3,4-dimethylphenyl group, a4-cyclopropyl-3,5-dimethylphenyl group, a 2-ethinyl-3-methylphenylgroup, a 3-ethinyl-2-methylphenyl group, a 2-ethinyl-4-methylphenylgroup, a 4-ethinyl-2-methylphenyl group, a 3-ethinyl-4-methylphenylgroup, a 4-ethinyl-3-methylphenyl group, a 5-ethinyl-2-methylphenylgroup, a 2-ethinyl-5-methylphenyl group, a 2-ethinyl-6-methylphenylgroup, a 3-ethinyl-5-methylphenyl group, a 4-ethinyl-2,3-dimethylphenylgroup, a 3-ethinyl-2,4-dimethylphenyl group, a2-ethinyl-3,4-dimethyl-phenyl group, a 2-ethinyl-3,5-dimethylphenylgroup, a 3-ethinyl-2,5-dimethylphenyl group, a5-ethinyl-2,3-dimethylphenyl group, a 6-ethinyl-2,3-dimethylphenylgroup, a 3-ethinyl-2,6-dimethylphenyl group, a2-ethinyl-3,6-dimethylphenyl group, a 5-ethinyl-2,4-dimethylphenylgroup, a 4-ethinyl-2,5-dimethylphenyl group, a2-ethinyl-4,5-dimethylphenyl group, a 6-ethinyl-2,4-dimethylphenylgroup, a 4-ethinyl-2,6-dimethylphenyl group, a5-ethinyl-3,4-dimethylphenyl group, a 4-ethinyl-3,5-dimethylphenylgroup, a 2-methyl-3-nitrophenyl group, a 3-methyl-2-nitrophenyl group, a2-methyl-4-nitrophenyl group, a 4-methyl-2-nitrophenyl group, a3-methyl-4-nitrophenyl group, a 4-methyl-3-nitrophenyl group, a5-methyl-2-nitrophenyl group, a 2-methyl-5-nitrophenyl group, a2-methyl-6-nitrophenyl group, a 3-methyl-5-nitrophenyl group, a2,3-dimethyl-4-nitrophenyl group, a 2,4-dimethyl-3-nitrophenyl group, a3,4-dimethyl-2-nitrophenyl group, a 3,5-dimethyl-2-nitrophenyl group, a2,5-dimethyl-3-nitrophenyl group, a 2,3-dimethyl-5-nitrophenyl group, a2,3-dimethyl-6-nitrophenyl group, a 2,6-dimethyl-3-nitrophenyl group, a3,6-dimethyl-2-nitrophenyl group, a 2,4-dimethyl-5-nitrophenyl group, a2,5-dimethyl-4-nitrophenyl group, a 4,5-dimethyl-2-nitrophenyl group, a2,4-dimethyl-6-nitrophenyl group, a 2,6-dimethyl-4-nitrophenyl group, a3,4-dimethyl-5-nitrophenyl group, a 3,5-dimethyl-4-nitrophenyl group, a2-methyl-3-methoxyphenyl group, a 3-methyl-2-methoxyphenyl group, a2-methyl-4-methoxyphenyl group, a 4-methyl-2-methoxyphenyl group, a3-methyl-4-methoxyphenyl group, a 4-methyl-3-methoxyphenyl group, a5-methyl-2-methoxyphenyl group, a 2-methyl-5-methoxyphenyl group, a2-methyl-6-methoxyphenyl group, a 3-methyl-5-methoxyphenyl group, a2,3-dimethyl-4-methoxyphenyl group, a 2,4-dimethyl-3-methoxyphenylgroup, a 3,4-dimethyl-2-methoxyphenyl group, a3,5-dimethyl-2-methoxyphenyl group, a 2,5-dimethyl-3-methoxyphenylgroup, a 2,3-dimethyl-5-methoxyphenyl group, a2,3-dimethyl-6-methoxyphenyl group, a 2,6-dimethyl-3-methoxyphenylgroup, a 3,6-dimethyl-2-methoxyphenyl group, a2,4-dimethyl-5-methoxyphenyl group, a 2,5-dimethyl-4-methoxyphenylgroup, a 4,5-dimethyl-2-methoxyphenyl group, a2,4-dimethyl-6-methoxyphenyl group, a 2,6-dimethyl-4-methoxyphenylgroup, a 3,4-dimethyl-5-methoxyphenyl group, a3,5-dimethyl-4-methoxyphenyl group, a 2-cyano-3-ethylphenyl group, a3-cyano-2-ethylphenyl group, a 2-cyano-4-ethylphenyl group, a4-cyano-2-ethylphenyl group, a 3-cyano-4-ethylphenyl group, a4-cyano-3-ethylphenyl group, a 5-cyano-2-ethylphenyl group, a2-cyano-5-ethylphenyl group, a 2-cyano-6-ethylphenyl group, a3-cyano-5-ethylphenyl group, a 4-cyano-2,3-diethylphenyl group, a3-cyano-2,4-diethylphenyl group, a 2-cyano-3,4-diethylphenyl group, a2-cyano-3,5-diethylphenyl group, a 3-cyano-2,5-diethylphenyl group, a5-cyano-2,3-diethylphenyl group, a 6-cyano-2,3-diethylphenyl group, a3-cyano-2,6-diethylphenyl group, a 2-cyano-3,6-diethylphenyl group, a5-cyano-2,4-diethylphenyl group, a 4-cyano-2,5-diethylphenyl group, a2-cyano-4,5-diethylphenyl group, a 6-cyano-2,4-diethylphenyl group, a4-cyano-2,6-diethylphenyl group, a 5-cyano-3,4-diethylphenyl group, a4-cyano-3,5-diethylphenyl group, a 2-ethyl-3-trifluoromethylphenylgroup, a 3-ethyl-2-trifluoromethylphenyl group, a2-ethyl-4-trifluoromethylphenyl group, a 4-ethyl-2-trifluoromethylphenylgroup, a 3-ethyl-4-trifluoromethylphenyl group, a4-ethyl-3-trifluoromethylphenyl group, a 5-ethyl-2-trifluoromethylphenylgroup, a 2-ethyl-5-trifluoromethylphenyl group, a2-ethyl-6-trifluoromethylphenyl group, a 3-ethyl-5-trifluoromethylphenylgroup, 2,3-diethyl-4-trifluoromethylphenyl group,2,4-diethyl-3-trifluoromethylphenyl group,3,4-diethyl-2-trifluoromethylphenyl group,3,5-diethyl-2-trifluoromethylphenyl group,2,5-diethyl-3-trifluoromethylphenyl group,2,3-diethyl-5-trifluoromethylphenyl group,2,3-diethyl-6-trifluoromethylphenyl group,2,6-diethyl-3-trifluoromethylphenyl group,3,6-diethyl-2-trifluoromethylphenyl group,2,4-diethyl-5-trifluoromethylphenyl group,2,5-diethyl-4-trifluoromethylphenyl group,4,5-diethyl-2-trifluoromethylphenyl group, a2,4-diethyl-6-trifluoromethylphenyl group, a2,6-diethyl-4-trifluoromethylphenyl group, a3,4-diethyl-5-trifluoromethylphenyl group, a3,5-diethyl-4-trifluoromethylphenyl group, a 2-cyclopropyl-3-ethylphenylgroup, a 3-cyclopropyl-2-ethylphenyl group, a2-cyclopropyl-4-ethylphenyl group, a 4-cyclopropyl-2-ethylphenyl group,a 3-cyclopropyl-4-ethylphenyl group, a 4-cyclopropyl-3-ethylphenylgroup, a 5-cyclopropyl-2-ethylphenyl group, a2-cyclopropyl-5-ethylphenyl group, a 2-cyclopropyl-6-ethylphenyl group,a 3-cyclopropyl-5-ethylphenyl group, a 4-cyclopropyl-2,3-diethylphenylgroup, a 3-cyclopropyl-2,4-diethylphenyl group, a2-cyclopropyl-3,4-diethylphenyl group, a 2-cyclopropyl-3,5-diethylphenylgroup, a 3-cyclopropyl-2,5-diethylphenyl group, a5-cyclopropyl-2,3-diethylphenyl group, a 6-cyclopropyl-2,3-diethylphenylgroup, a 3-cyclopropyl-2,6-diethylphenyl group, a2-cyclopropyl-3,6-diethylphenyl group, a 5-cyclopropyl-2,4-diethylphenylgroup, a 4-cyclopropyl-2,5-diethylphenyl group, a2-cyclopropyl-4,5-diethylphenyl group, a 6-cyclopropyl-2,4-diethylphenylgroup, a 4-cyclopropyl-2,6-diethylphenyl group, a5-cyclopropyl-3,4-diethylphenyl group, a 4-cyclopropyl-3,5-diethylphenylgroup, a 2-ethyl-3-ethinylphenyl group, a 3-ethyl-2-ethinylphenyl group,a 2-ethyl-4-ethinylphenyl group, a 4-ethyl-2-ethinylphenyl group, a3-ethyl-4-ethinylphenyl group, a 4-ethyl-3-ethinylphenyl group, a5-ethyl-2-ethinylphenyl group, a 2-ethyl-5-ethinylphenyl group, a2-ethyl-6-ethinylphenyl group, a 3-ethyl-5-ethinylphenyl group, a2,3-diethyl-4-ethinylphenyl group, a 2,4-diethyl-3-ethinylphenyl group,a 3,4-diethyl-2-ethinylphenyl group, a 3,5-diethyl-2-ethinylphenylgroup, a 2,5-diethyl-3-ethinylphenyl group, a2,3-diethyl-5-ethinylphenyl group, a 2,3-diethyl-6-ethinylphenyl group,a 2,6-diethyl-3-ethinylphenyl group, a 3,6-diethyl-2-ethinylphenylgroup, a 2,4-diethyl-5-ethinylphenyl group, a2,5-diethyl-4-ethinylphenyl group, a 4,5-diethyl-2-ethinylphenyl group,a 2,4-diethyl-6-ethinylphenyl group, a 2,6-diethyl-4-ethinylphenylgroup, a 3,4-diethyl-5-ethinylphenyl group, a3,5-diethyl-4-ethinylphenyl group, a 2-ethyl-3-nitrophenyl group, a3-ethyl-2-nitrophenyl group, a 2-ethyl-4-nitrophenyl group, a4-ethyl-2-nitrophenyl group, a 3-ethyl-4-nitrophenyl group, a4-ethyl-3-nitrophenyl group, a 5-ethyl-2-nitrophenyl group, a2-ethyl-5-nitrophenyl group, a 2-ethyl-6-nitrophenyl group, a3-ethyl-5-nitrophenyl group, a 2,3-diethyl-4-nitrophenyl group, a2,4-diethyl-3-nitrophenyl group, a 2,3-diethyl-5-nitrophenyl group, a2,3-diethyl-6-nitrophenyl group, a 2,6-diethyl-3-nitrophenyl group, a3,6-diethyl-2-nitrophenyl group, a 2,4-diethyl-5-nitrophenyl group, a2,5-diethyl-4-nitrophenyl group, a 4,5-diethyl-2-nitrophenyl group, a2,4-diethyl-6-nitrophenyl group, a 2,6-diethyl-4-nitrophenyl group,3,4-diethyl-5-nitrophenyl group, a 3,5-diethyl-4-nitrophenyl group, a2-ethyl-3-methoxyphenyl group, a 3-ethyl-2-methoxyphenyl group, a2-ethyl-4-methoxyphenyl group, a 4-ethyl-2-methoxyphenyl group, a3-ethyl-4-methoxyphenyl group, a 4-ethyl-3-methoxyphenyl group, a5-ethyl-2-methoxyphenyl group, a 2-ethyl-5-methoxyphenyl group, a2-ethyl-6-methoxyphenyl group, a 3-ethyl-5-methoxyphenyl group, a2,3-diethyl-4-methoxyphenyl group, a 2,4-diethyl-3-methoxyphenyl group,a 3,4-diethyl-2-methoxyphenyl group, a 3,5-diethyl-2-methoxyphenylgroup, a 2,5-diethyl-3-methoxyphenyl group, a2,3-diethyl-5-methoxyphenyl group, a 2,3-diethyl-6-methoxyphenyl group,a 2,6-diethyl-3-methoxyphenyl group, a 3,6-diethyl-2-methoxyphenylgroup, a 2,4-diethyl-5-methoxyphenyl group, a2,5-diethyl-4-methoxyphenyl group, a 4,5-diethyl-2-methoxyphenyl group,a 2,4-diethyl-6-methoxyphenyl group, a 2,6-diethyl-4-methoxyphenylgroup, a 3,4-diethyl-5-methoxyphenyl group, a3,5-diethyl-4-methoxyphenyl group, a 2-chloro-3-trifluoromethylphenylgroup, a 3-chloro-2-trifluoromethylphenyl group, a2-chloro-4-trifluoromethylphenyl group, a4-chloro-2-trifluoromethylphenyl group, a 3-chloro-4-trifluoromethylgroup, a 3-chloro-4-trifluoromethyl group, a 4-chloro-3-trifluoromethylgroup, a 5-chloro-2-trifluoromethyl group, a 2-chloro-5-trifluoromethylgroup, a 2-chloro-6-trifluoromethyl group, a 3-chloro-5-trifluoromethylgroup, a 2,3-dichloro-4-trifluoromethyl group, a2,4-dichloro-3-trifluoromethyl group, a 3,4-dichloro-2-trifluoromethylgroup, a 2,5-dichloro-3-trifluoromethyl group, a2,3-dichloro-5-trifluoromethyl group, a 2,6-dichloro-3-trifluoromethylgroup, a 3,6-dichloro-2-trifluoromethyl group, a2,4-dichloro-5-trifluoromethyl group, a 2,5-dichloro-4-trifluoromethylgroup, a 4,5-dichloro-2-trifluoromethyl group, a2,4-dichloro-6-trifluoromethyl group, a 2,6-dichloro-4-trifluoromethylgroup, a 3,4-dichloro-5-trifluoromethyl group, a3,5-dichloro-4-trifluoromethyl group, a 2-chloro-3-cyclopropylphenylgroup, a 3-chloro-2-cyclopropylphenyl group, a2-chloro-4-cyclopropylphenyl group, a 4-chloro-2-cyclopropylphenylgroup, a 3-chloro-4-cyclopropylphenyl group, a4-chloro-3-cyclopropylphenyl group, a 5-chloro-2-cyclopropylphenylgroup, a 2-chloro-5-cyclopropylphenyl group, a2-chloro-6-cyclopropylphenyl group, a 3-chloro-6-cyclopropylphenylgroup, a 2,3-dichloro-4-cyclopropylphenyl group, a2,4-dichloro-3-cyclopropylphenyl group, a3,4-dichloro-2-cyclopropylphenyl group, a3,5-dichloro-2-cyclopropylphenyl group, a2,5-dichloro-3-cyclopropylphenyl group, a2,3-dichloro-5-cyclopropylphenyl group, a2,3-dichloro-6-cyclopropylphenyl group, a2,6-dichloro-3-cyclopropylphenyl group, a3,6-dichloro-2-cyclopropylphenyl group, a2,4-dichloro-5-cyclopropylphenyl group, a2,5-dichloro-4-cyclopropylphenyl group, a4,5-dichloro-2-cyclopropylphenyl group, a2,4-dichloro-6-cyclopropylphenyl group, a2,6-dichloro-4-cyclopropylphenyl group, a3,4-dichloro-5-cyclopropylphenyl group, a 3,5-chloro-4-cyclopropylphenylgroup, a 2-ethoxy-3-fluorophenyl group, a 3-ethoxy-2-fluorophenyl group,a 2-ethoxy-4-fluorophenyl group, a 4-ethoxy-2-fluorophenyl group, a3-ethoxy-4-fluorophenyl group, a 4-ethoxy-3-fluorophenyl group, a5-ethoxy-2-fluorophenyl group, a 2-ethoxy-5-fluorophenyl group, a2-ethoxy-6-fluorophenyl group, a 3-ethoxy-5-fluorophenyl group, a4-ethoxy-2,3-difluorophenyl group, a 3-ethoxy-2,4-difluorophenyl group,a 2-ethoxy-3,4-difluorophenyl group, a 2-ethoxy-3,5-difluorophenylgroup, a 3-ethoxy-2,5-difluorophenyl group, a5-ethoxy-2,3-difluorophenyl group, a 6-ethoxy-2,3-difluorophenyl group,a 3-ethoxy-2,6-difluorophenyl group, a 2-ethoxy-3,6-difluorophenylgroup, a 5-ethoxy-2,4-difluorophenyl group, a4-ethoxy-2,5-difluorophenyl group, a 2-ethoxy-4,5-difluorophenyl group,a 6-ethoxy-2,4-difluorophenyl group, a 4-ethoxy-2,6-difluorophenylgroup, a 5-ethoxy-3,4-difluorophenyl group, a4-ethoxy-3,5-difluorophenyl group, a 2-bromo-3-trifluoromethoxyphenylgroup, a 3-bromo-2-trifluoromethoxyphenyl group, a2-bromo-4-trifluoromethoxyphenyl group, a4-bromo-2-trifluoromethoxyphenyl group, a3-bromo-4-trifluoromethoxyphenyl group, a4-bromo-3-trifluoromethoxyphenyl group, a5-bromo-2-trifluoromethoxyphenyl group, a2-bromo-5-trifluoromethoxyphenyl group, a2-bromo-6-trifluoromethoxyphenyl group, a3-bromo-5-trifluoromethoxyphenyl group, a2,3-dibromo-4-trifluoromethoxyphenyl group, a2,4-dibromo-3-trifluoromethoxyphenyl group, a3,4-dibromo-2-trifluoromethoxyphenyl group, a3,5-dibromo-2-trifluoromethoxyphenyl group, a2,5-dibromo-3-trifluoromethoxyphenyl group, a2,3-dibromo-5-trifluoromethoxyphenyl group, a2,3-dibromo-6-trifluoromethoxyphenyl group, a2,6-dibromo-3-trifluoromethoxyphenyl group, a3,6-dibromo-2-trifluoromethoxyphenyl group, a2,4-dibromo-5-trifluoromethoxyphenyl group, a2,5-dibromo-4-trifluoromethoxyphenyl group, a4,5-dibromo-2-trifluoromethoxyphenyl group, a2,4-dibromo-6-trifluoromethoxyphenyl group, a2,6-dibromo-4-trifluoromethoxyphenyl group, a3,4-dibromo-5-trifluoromethoxyphenyl group, a3,5-dibromo-4-trifluoromethoxyphenyl group, a 4-chloro-2,6-diethylphenylgroup, a 2-bromo-4,6-dimethylphenyl group, a4,6-dimethyl-2-methoxyphenyl group, a 2-bromo-4,6-dimethylphenyl group,a 4-bromo-2,6-diethylphenyl group, a 4-ethinyl-2,6-dimethylphenyl group,a 2,6-diethyl-4-methoxyphenyl group, a 2,6-diethyl-4-nitrophenyl group,a 2,6-diethyl-4-ethinylphenyl group, a 2-cyano-4,6-dimethylphenyl group,a 2-cyano-4,6-diethylphenyl group, a 2-cyano-6-ethyl-4-methylphenylgroup, a 2,4-dichloro-6-methylphenyl group, a2-chloro-4,6-dimethylphenyl group, a 2-chloro-6-ethyl-4-methylphenylgroup, a 2-chloro-6-ethyl-4-methoxyphenyl group, a2,4-dichloro-6-ethylphenyl group, a 2-bromo-6-ethyl-4-methylphenylgroup, a 2-ethyl-4-methyl-6-methoxyphenyl group, a3-ethyl-5-ethinylbiphenyl-4-yl group, a 3-ethyl-5-methoxybiphenyl-4-ylgroup, a 2-cyclopropyl-6-ethyl-4-methylphenyl group, a4-cyclopropyl-2,6-diethylphenyl group, a2-chloro-6-fluoro-3-methylphenyl group, a2-bromo-4-chloro-6-methylphenyl group, a 2-bromo-6-chloro-4-methylphenylgroup, a 2-bromo-4-chloro-6-trifluoromethoxyphenyl group, a2-chloro-6-cyclopropyl-4-methylphenyl group, a4-bromo-2-chloro-6-trifluoromethoxyphenyl group, a2-chloro-6-fluoro-3-methylphenyl group, a 3,5-diethylbiphenyl-4-ylgroup, a 4′-chloro-3,5-diethylbiphenyl-4-yl group, a4′-methyl-3,5-diethylbiphenyl-4-yl group, a 4-methylbiphenyl-3-yl group,a 4-ethylbiphenyl-3-yl group, a 4-propylbiphenyl-3-yl group, a4-cyclopropylbiphenyl-3-yl group, a 4-bromobiphenyl-3-yl group, a4-iodobiphenyl-3-yl group, a 2′-fluoro-4-methylbiphenyl-3-yl group, a4-ethyl-2′-fluorobiphenyl-3-yl group, a 2′-fluoro-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-2′-fluorobiphenyl-3-yl group, a4,2′-difluorobiphenyl-3-yl group, a 4-chloro-2′-fluorobiphenyl-3-ylgroup, a 4-bromo-2′-fluorobiphenyl-3-yl group, a2′-fluoro-4-iodobiphenyl-3-yl group, a 2′-chloro-4-methylbiphenyl-3-ylgroup, a 2′-chloro-4-ethylbiphenyl-3-yl group, a2′-chloro-4-propylbiphenyl-3-yl group, a2′-chloro-4-cyclopropylbiphenyl-3-yl group, a2′-chloro-4-fluorobiphenyl-3-yl group, a 4,2′-dichlorobiphenyl-3-ylgroup, a 4-bromo-2′-chlorobiphenyl-3-yl group, a2′-chloro-4-iodobiphenyl-3-yl group, a 2′-bromo-4-methylbiphenyl-3-ylgroup, a 2′-bromo-4-ethylbiphenyl-3-yl group, a2′-bromo-4-propylbiphenyl-3-yl group, a2′-bromo-4-cyclopropylbiphenyl-3-yl group, a2′-bromo-4-fluorobiphenyl-3-yl group, a 2′-bromo-4-chlorobiphenyl-3-ylgroup, a 4,2′-dibromobiphenyl-3-yl group, a 2′-bromo-4-iodobiphenyl-3-ylgroup, a 2′-iodo-4-methylbiphenyl-3-yl group, a4-ethyl-2′-iodobiphenyl-3-yl group, a 2′-iodo-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-2′-iodobiphenyl-3-yl group, a2′-iodo-4-propylbiphenyl-3-yl group, a4-cyclopropyl-2′-iodobiphenyl-3-yl group, a4-fluoro-2′-iodobiphenyl-3-yl group, a 4-chloro-2′-iodobiphenyl-3-ylgroup, a 4-bromo-2′-iodobiphenyl-3-yl group, a 4,2′-diiodobiphenyl-3-ylgroup, a 4,2′-dimethylbiphenyl-3-yl group, a4-ethyl-2′-methylbiphenyl-3-yl group, a 2′-methyl-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-2′-methylbiphenyl-3-yl group, a4-fluoro-2′-methylbiphenyl-3-yl group, a 4-chloro-2′-methylbiphenyl-3-ylgroup, a 4-bromo-2′-methylbiphenyl-3-yl group, a4-iodo-2′-methylbiphenyl-3-yl group, a 2′-ethyl-4-methylbiphenyl-3-ylgroup, a 4,2′-diethylbiphenyl-3-yl group, a2′-ethyl-4-propylbiphenyl-3-yl group, a4-cyclopropyl-2′-ethylbiphenyl-3-yl group, a2′-ethyl-4-fluorobiphenyl-3-yl group, a 4-chloro-2′-ethylbiphenyl-3-ylgroup, a 4-bromo-2′-ethylbiphenyl-3-yl group, a2′-ethyl-4-iodobiphenyl-3-yl group, a4-methyl-2′-trifluoromethylbiphenyl-3-yl group, a4-ethyl-2′-trifluoromethylbiphenyl-3-yl group, a4-propyl-2′-trifluoromethylbiphenyl-3-yl group, a4-cyclopropyl-2′-trifluoromethylbiphenyl-3-yl group, a4-fluoro-2′-trifluoromethylbiphenyl-3-yl group, a4-chloro-2′-trifluoromethylbiphenyl-3-yl group, a4-bromo-2′-trifluoromethylbiphenyl-3-yl group, a4-iodo-2′-trifluoromethylbiphenyl-3-yl group, a2′-methoxy-4-methylbiphenyl-3-yl group, a4-ethyl-2′-methoxybiphenyl-3-yl group, a2′-methoxy-4-propylbiphenyl-3-yl group, a4-cyclopropyl-2′-methoxybiphenyl-3-yl group, a4-fluoro-2′-methoxybiphenyl-3-yl group, a4-chloro-2′-methoxybiphenyl-3-yl group, a4-bromo-2′-methoxybiphenyl-3-yl group, a 4-iodo-2′-methoxybiphenyl-3-ylgroup, a 4-methyl-2′-trifluoromethoxybiphenyl-3-yl group, a4-ethyl-2′-trifluoromethoxybiphenyl-3-yl group, a4-propyl-2′-trifluoromethoxybiphenyl-3-yl group, a4-cyclopropyl-2′-trifluoromethoxybiphenyl-3-yl group, a4-fluoro-2′-trifluoromethoxybiphenyl-3-yl group, a4-chloro-2′-trifluoromethoxybiphenyl-3-yl group, a4-bromo-2′-trifluoromethoxybiphenyl-3-yl group, a4-iodo-2′-trifluoromethoxybiphenyl-3-yl group, a3′-fluoro-4-methylbiphenyl-3-yl group, a 4-ethyl-3′-fluorobiphenyl-3-ylgroup, a 3′-fluoro-4-propylbiphenyl-3-yl group, a4-cyclopropyl-3′-fluorobiphenyl-3-yl group, a 4,3′-difluorobiphenyl-3-ylgroup, a 4-chloro-3′-fluorobiphenyl-3-yl group, a4-bromo-3′-fluorobiphenyl-3-yl group, a 3′-fluoro-4-iodobiphenyl-3-ylgroup, a 3′-chloro-4-methylbiphenyl-3-yl group, a3′-chloro-4-ethylbiphenyl-3-yl group, a 3′-chloro-4-propylbiphenyl-3-ylgroup, a 3′-chloro-4-cyclopropylbiphenyl-3-yl group, a3′-chloro-4-fluorobiphenyl-3-yl group, a 4,3′-dichlorobiphenyl-3-ylgroup, a 4-bromo-3′-chlorobiphenyl-3-yl group, a3′-chloro-4-iodobiphenyl-3-yl group, a 3′-bromo-4-methylbiphenyl-3-ylgroup, a 3′-bromo-4-ethylbiphenyl-3-yl group, a3′-bromo-4-propylbiphenyl-3-yl group, a3′-bromo-4-cyclopropylbiphenyl-3-yl group, a3′-bromo-4-fluorobiphenyl-3-yl group, a 3′-bromo-4-chlorobiphenyl-3-ylgroup, a 4,3′-dibromobiphenyl-3-yl group, a 3′-bromo-4-iodobiphenyl-3-ylgroup, a 3′-iodo-4-methylbiphenyl-3-yl group, a4,3′-dibromobiphenyl-3-yl group, a 3′-bromo-4-iodobiphenyl-3-yl group, a3′-iodo-4-methylbiphenyl-3-yl group, a 4-ethyl-3′-iodobiphenyl-3-ylgroup, a 3′-iodo-4-propylbiphenyl-3-yl group, a4-cyclopropyl-3′-iodobiphenyl-3-yl group, a4-fluoro-3′-iodobiphenyl-3-yl group, a 4-chloro-3′-iodobiphenyl-3-ylgroup, a 4-bromo-3′-iodobiphenyl-3-yl group, a 4,3′-diiodobiphenyl-3-ylgroup, a 4,3′-dimethylbiphenyl-3-yl group, a4-ethyl-3′-methylbiphenyl-3-yl group, a 3′-methyl-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-3′-methylbiphenyl-3-yl group, a4-fluoro-3′-methylbiphenyl-3-yl group, a 4-chloro-3′-methylbiphenyl-3-ylgroup, a 4-bromo-3′-methylbiphenyl-3-yl group, a4-iodo-3′-methylbiphenyl-3-yl group, a 3′-ethyl-4-methylbiphenyl-3-ylgroup, a 4,3′-diethylbiphenyl-3-yl group, a3′-ethyl-4-propylbiphenyl-3-yl group, a4-cyclopropyl-3′-ethylbiphenyl-3-yl group, a3′-ethyl-4-fluorobiphenyl-3-yl group, a 4-chloro-3′-ethylbiphenyl-3-ylgroup, a 4-bromo-3′-ethylbiphenyl-3-yl group, a3′-ethyl-4-iodobiphenyl-3-yl group, a4-methyl-3′-trifluoromethylbiphenyl-3-yl group, a4-ethyl-3′-trifluoromethylbiphenyl-3-yl group, a4-propyl-3′-trifluoromethylbiphenyl-3-yl group, a4-cyclopropyl-3′-trifluoromethylbiphenyl-3-yl group, a4-fluoro-3′-trifluoromethylbiphenyl-3-yl group, a4-chloro-3′-trifluoromethylbiphenyl-3-yl group, a4-bromo-3′-trifluoromethylbiphenyl-3-yl group, a4-iodo-3′-trifluoromethylbiphenyl-3-yl group, a3′-methoxy-4-methylbiphenyl-3-yl group, a4-ethyl-3′-methoxybiphenyl-3-yl group, a3′-methoxy-4-propylbiphenyl-3-yl group, a4-cyclopropyl-3′-methoxybiphenyl-3-yl group, a4-fluoro-3′-methoxybiphenyl-3-yl group, a4-chloro-3′-methoxybiphenyl-3-yl group, a4-bromo-3′-methoxybiphenyl-3-yl group, a 4-iodo-3′-methoxybiphenyl-3-ylgroup, a 4-methyl-3′-trifluoromethoxybiphenyl-3-yl group, a4-ethyl-3′-trifluoromethoxybiphenyl-3-yl group, a4-propyl-3′-trifluoromethoxybiphenyl-3-yl group, a4-cyclopropyl-3′-trifluoromethoxybiphenyl-3-yl group, a4-fluoro-3′-trifluoromethoxybiphenyl-3-yl group, a4-chloro-3′-trifluoromethoxybiphenyl-3-yl group, a4-bromo-3′-trifluoromethoxybiphenyl-3-yl group, a4-iodo-3′-trifluoromethoxybiphenyl-3-yl group, a 4-methylbiphenyl-3-ylgroup, a 4-ethylbiphenyl-3-yl group, a 4-propylbiphenyl-3-yl group, a4-cyclopropylbiphenyl-3-yl group, a 4-fluorobiphenyl-3-yl group, a4-chlorobiphenyl-3-yl group, a 4-bromobiphenyl-3-yl group, a4-iodobiphenyl-3-yl group, a 4′-fluoro-4-methylbiphenyl-3-yl group, a4-ethyl-4′-fluorobiphenyl-3-yl group, a 4′-fluoro-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-4′-fluorobiphenyl-3-yl group, a4,4′-difluorobiphenyl-3-yl group, a 4-chloro-4′-fluorobiphenyl-3-ylgroup, a 4-bromo-4′-fluorobiphenyl-3-yl group, a4′-fluoro-4-iodobiphenyl-3-yl group, a 4′-chloro-4-methylbiphenyl-3-ylgroup, a 4′-chloro-4-ethylbiphenyl-3-yl group, a4′-chloro-4-propylbiphenyl-3-yl group, a4′-chloro-4-cyclopropylbiphenyl-3-yl group, a4′-chloro-4-fluorobiphenyl-3-yl group, a 4,4′-dichlorobiphenyl-3-ylgroup, a 4-bromo-4′-chlorobiphenyl-3-yl group, a4′-chloro-4-iodobiphenyl-3-yl group, a 4′-bromo-4-methylbiphenyl-3-ylgroup, a 4′-bromo-4-ethylbiphenyl-3-yl group, a4′-bromo-4-propylbiphenyl-3-yl group, a4′-bromo-4-cyclopropylbiphenyl-3-yl group, a4′-bromo-4-fluorobiphenyl-3-yl group, a 4′-bromo-4-chlorobiphenyl-3-ylgroup, a 4,4′-dibromobiphenyl-3-yl group, a 4′-bromo-4-iodobiphenyl-3-ylgroup, a 4′-iodo-4-methylbiphenyl-3-yl group, a4-ethyl-4′-iodophenyl-3-yl group, a 4′-iodo-4-propylbiphenyl-3-yl group,a 4-cyclopropyl-4′-iodobiphenyl-3-yl group, a4-fluoro-4′-iodobiphenyl-3-yl group, a 4-chloro-4′-iodobiphenyl-3-ylgroup, a 4-bromo-4′-iodobiphenyl-3-yl group, a 4,4′-diiodobiphenyl-3-ylgroup, a 4,4′-dimethylbiphenyl-3-yl group, a4-ethyl-4′-methylbiphenyl-3-yl group, a 4′-methyl-4-propylbiphenyl-3-ylgroup, a 4-cyclopropyl-4′-methylbiphenyl-3-yl group, a4-fluoro-4′-methylbiphenyl-3-yl group, a 4-chloro-4′-methylbiphenyl-3-ylgroup, a 4-bromo-4′-methylbiphenyl-3-yl group, a4-iodo-4′-methylbiphenyl-3-yl group, a 4′-ethyl-4-methylbiphenyl-3-ylgroup, a 4,4′-diethylbiphenyl-3-yl group, a4′-ethyl-4-propylbiphenyl-3-yl group, a4-cyclopropyl-4′-ethylbiphenyl-3-yl group, a4′-ethyl-4-fluorobiphenyl-3-yl group, a 4-chloro-4′-ethylbiphenyl-3-ylgroup, a 4-bromo-4′-ethylbiphenyl-3-yl group, a4′-ethyl-4-iodobiphenyl-3-yl group, a4-methyl-4′-trifluoromethylbiphenyl-3-yl group, a4-ethyl-4′-trifluoromethylbiphenyl-3-yl group, a4-propyl-4′-trifluoromethylbiphenyl-3-yl group, a4-cyclopropyl-4′-trifluoromethylbiphenyl-3-yl group, a4-fluoro-4′-trifluoromethylbiphenyl-3-yl group, a4-chloro-4′-trifluoromethylbiphenyl-3-yl group, a4-bromo-4′-trifluoromethylbiphenyl-3-yl group, a4-iodo-4′-trifluoromethylbiphenyl-3-yl group, a4′-methoxy-4-methylbiphenyl-3-yl group, a4-ethyl-4′-methoxybiphenyl-3-yl group, a4′-methoxy-4-propylbiphenyl-3-yl group, a4-cyclopropyl-4′-methoxybiphenyl-3-yl group, a4-fluoro-4′-methoxybiphenyl-3-yl group, a4-chloro-4′-methoxybiphenyl-3-yl group, a4-bromo-4′-methoxybiphenyl-3-yl group, a 4-iodo-4′-methoxybiphenyl-3-ylgroup, a 4-methyl-4′-trifluoromethoxybiphenyl-3-yl group, a4-ethyl-4′-trifluoromethoxybiphenyl-3-yl group, a4-propyl-4′-trifluoromethoxybiphenyl-3-yl group, a4-cyclopropyl-4′-trifluoromethoxybiphenyl-3-yl group, a4-fluoro-4′-trifluoromethoxybiphenyl-3-yl group, a4-chloro-4′-trifluoromethoxybiphenyl-3-yl group, a4-bromo-4′-trifluoromethoxybiphenyl-3-yl group, a4-iodo-4′-trifluoromethoxybiphenyl-3-yl group, a 2-methylnaphthalen-1-ylgroup, a 3-methylnaphthalen-1-yl group, an 8-methylnaphthalen-1-ylgroup, a 1-methylnaphthalen-2-yl group, a 3-methylnaphthalen-2-yl group,a 4-methylnaphthalen-2-yl group, a 2-ethylnaphthalen-1-yl group, a3-ethylnaphthalen-1-yl group, an 8-ethylnaphthalen-1-yl group, a1-ethylnaphthalen-2-yl group, a 3-ethylnaphthalen-2-yl group, a4-ethylnaphthalen-2-yl group, a 2-fluoronaphthalen-1-yl group, a3-fluoronaphthalen-1-yl group, an 8-fluoronaphthalen-1-yl group, a1-fluoronaphthalen-2-yl group, a 3-fluoronaphthalen-2-yl group, a4-fluoronaphthalen-2-yl group, a 2-chloronaphthalen-1-yl group, a3-chloronaphthalen-1-yl group, an 8-chloronaphthalen-1-yl group, a1-chloronaphthalen-2-yl group, a 3-chloronaphthalen-2-yl group, a4-chloronaphthalen-2-yl group, a 2-bromonaphthalen-1-yl group, a3-bromonaphthalen-1-yl group, an 8-bromonaphthalen-1-yl group, a1-bromonaphthalen-2-yl group, a 3-bromonaphthalen-2-yl group, a4-bromonaphthalen-2-yl group, a 2-iodonaphthalen-1-yl group, a3-iodonaphthalen-1-yl group, an 8-iodonaphthalen-1-yl group, a1-iodonaphthalen-2-yl group, a 3-iodonaphthalen-2-yl group, a4-iodonaphthalen-2-yl group, a 2-trifluoromethylnaphthalen-1-yl group, a3-trifluoromethylnaphthalen-1-yl group, and8-trifluoromethylnaphthalen-1-yl group, a1-trifluoromethylnaphthalen-2-yl group, a3-trifluoromethylnaphthalen-2-yl group, a4-trifluoromethylnaphthalen-2-yl group, a 2-methoxynaphthalen-1-ylgroup, a 3-methoxynaphthalen-1-yl group, an 8-methoxynaphthalen-1-ylgroup, a 1-methoxynaphthalen-2-yl group, a 3-methoxynaphthalen-2-ylgroup, a 4-methoxynaphthalen-2-yl group, a 2-cyclopropylnaphthalen-1-ylgroup, a 3-cyclopropylnaphthalen-1-yl group, an8-cyclopropylnaphthalen-1-yl group, a 1-cyclopropylnaphthalen-2-ylgroup, a 3-cyclopropylnaphthalen-2-yl group, a4-cyclopropylnaphthalen-2-yl group, a 2-ethinylnaphthalen-1-yl group, a3-ethinylnaphthalen-1-yl group, an 8-ethinylnaphthalen-1-yl group, a1-ethinylnaphthalen-2-yl group, a 3-ethinylnaphthalen-2-yl group, and a4-ethinylnaphthalen-2-yl group;

5- or 6-membered heteroaryl group optionally having one or moresubstituents: a 1-pyrazolyl group, a 2-pyrazolyl group, a 3-pyrazolylgroup, a 5-methyl-1-pyrazolyl group, a 5-ethyl-1-pyrazolyl group, a3-phenyl-5-ethyl-1-pyrazolyl group, a3-(4-chlorophenyl)-5-methyl-1-pyrazolyl group, a3-(4-chlorophenyl)-5-ethyl-1-pyrazolyl group, a3-(4-bromophenyl)-5-methyl-1-pyrazolyl group, a3-(4-bromophenyl)-5-ethyl-1-pyrazolyl group, a3-(4-chlorophenyl)-5-ethyl-1-pyrazolyl group, a3-(4-bromophenyl)-5-methyl-1-pyrazolyl group, a3-(4-bromophenyl)-5-ethyl-1-pyrazolyl group, a3-(4-trifluoromethylphenyl)-5-methyl-1-pyrazolyl group, a3-(4-trifluoromethylphenyl)-5-ethyl-1-pyrazolyl group, a 1-imidazolylgroup, a 2-methyl-1-imidazolyl group, a 2-ethyl-1-imidazolyl group, a2-methyl-4-phenyl-1-imidazolyl group, a 2-ethyl-4-phenyl-1-imidazolylgroup, a 2-methyl-4-(4-chlorophenyl)-1-imidazolyl group, a2-ethyl-4-(4-chlorophenyl)-1-imidazolyl group, a2-methyl-4-(4-bromophenyl)-1-imidazolyl group, a2-ethyl-4-(4-bromophenyl)-1-imidazolyl group, a2-methyl-4-(4-trifluoromethylphenyl)-1-imidazolyl group, a2-ethyl-4-(4-trifluoromethylphenyl)-1-imidazolyl group, a 2-imidazolylgroup, a 4-imidazolyl group, a 1-(1,2,4-triazolyl) group, a3-(1,2,4-triazolyl) group, a 5-(1,2,4-triazolyl) group, a 1-tetrazolylgroup, a 5-tetrazolyl group, a 2-oxazolyl group, a 4-oxazolyl group, a5-oxozolyl group, a 3-isoxazolylzolyl group, a 4-isoxazolylzolyl group,a 5-isoxazolylzolyl group, a 3-(1,2,4-oxadiazolyl) group, a5-(1,2,4-oxadiazolyl) group, a 2-(1,3,4-oxadiazolyl) group, a2-thiazolyl group, a 4-thiazolyl group, a 5-thiazolyl group, a3-isothiazolyl group, a 4-isothiazolyl group, a 5-isothiazolyl group, a3-(1,2,4-thiadiazolyl) group, a 5-(1,2,4-thiadiazolyl) group, a2-(1,3,4-thiadiazolyl) group, a 3-(1,2,5-thiadiazolyl) group, a 2-furylgroup, a 3-furyl group, a 2-thienyl group, a 3-thienyl group, a2-pyridyl group, a 3-pyridyl group, a 2-methyl-3-pyridyl group, a2-ethyl-3-pyridyl group, a 2-methyl-3-pyridyl group, a 2-ethyl-3-pyridylgroup, a 2-methyl-5-phenyl-3-pyridyl group, a 2-ethyl-5-phenyl-3-pyridylgroup, a 2-methyl-5-(4-chlorophenyl)-3-pyridyl group, a2-ethyl-5-(4-chlorophenyl)-3-pyridyl group, a2-methyl-5-(4-bromophenyl)-3-pyridyl group, a2-ethyl-5-(4-bromophenyl)-3-pyridyl group, a2-methyl-5-(4-trifluoromethylphenyl)-3-pyridyl group, a2-ethyl-5-(4-trifluoromethylphenyl)-3-pyridyl group, a 4-pyridyl group,a 3-methyl-4-pyridyl group, a 3-ethyl-4-pyridyl group, a2-phenyl-5-methyl-4-chlorophenyl)-5-ethyl-4-pyridyl pyridyl group, a2-phenyl-5-ethyl-4-pyridyl group, a2-(4-chlorophenyl)-5-methyl-4-pyridyl group, a2-(4-chlorophenyl)-5-ethyl-4-pyridyl group, a2-(4-bromophenyl)-5-methyl-4-pyridyl group, a2-(4-bromophenyl)-5-methyl-4-pyridyl group, a2-(4-bromophenyl)-5-ethyl-4-pyridyl group, a2-(4-trifluoromethylphenyl)-5-methyl-4-pyridyl group, a2-(4-trifluoromethylphenyl)-5-ethyl-4-pyridyl group, a 2-pyrimidylgroup, a 4-pyrimidyl group, a 5-pyrimidyl group, a 3-pyridazyl group, a4-pyridazyl group, a 3-methyl-4-pyridazyl group, a 3-ethyl-4-pyridazylgroup, a 3-methyl-6-phenyl-4-pyridazyl group, a3-ethyl-6-phenyl-3-pyridazyl group, a3-methyl-6-(4-chlorophenyl)-4-pyridazyl group, a3-ethyl-6-(4-chlorophenyl)-4-pyridazyl group, a3-methyl-6-(4-bromophenyl)-4-pyridazyl group, a3-ethyl-6-(4-bromophenyl)-4-pyridazyl group, a3-methyl-6-(4-trifluoromethylphenyl)-4-pyridazyl group, a3-ethyl-6-(4-trifluoromethylphenyl)-4-pyridazyl group, a 2-pyrazylgroup, a 3-methyl-2-pyrazyl group, a 3-ethyl-2-pyrazyl group, a3-methyl-6-phenyl-2-pyrazyl group, a 3-ethyl-6-phenyl-2-pyrazyl group, a3-methyl-6-(4-chlorophenyl)-2-pyrazyl group, a3-ethyl-6-(4-chlorophenyl)-2-pyrazyl group, a3-methyl-6-(4-bromophenyl)-2-pyrazyl group, a3-ethyl-6-(4-bromophenyl)-2-pyrazyl group, a3-methyl-6-(4-trifluoromethylphenyl)-2-pyrazyl group, a3-ethyl-6-(4-trifluoromethylphenyl)-2-pyrazyl group, and a2-(1,3,5-triazinyl) group;

8- to 10-membered fused heteroaryl group optionally having one or moresubstituents: an indol-1-yl group, an indol-2-yl group, an indol-3-ylgroup, an indol-4-yl group, an indol-5-yl group, an indol-6-yl group, anindol-7-yl group, a 1-methylindol-3-yl group, an indazol-1-yl group, anindazol-3-yl group, an indazol-4-yl group, an indazol-5-yl group, anindazol-6-yl group, an indazol-7-yl group, a benzotriazol-1-yl group, abenzotriazol-4-yl group, a benzotriazol-5-yl group, a benzotriazol-6-ylgroup, a benzotriazol-7-yl group, a benzofuran-2-yl group, abenzofuran-3-yl group, a benzofuran-4-yl group, a benzofuran-5-yl group,a benzofuran-6-yl group, a benzofuran-7-yl group, a benzothiophen-2-ylgroup, a benzothiophen-3-yl group, a benzothiophen-4-yl group, abenzothiophen-5-yl group, a benzothiophen-6-yl group, and abenzothiophen-7-yl group;

C1-C6 alkylsulfonyloxy group: a methylsulfonyloxy group, anethylsulfonyloxy group, a propylsulfonyloxy group, and ahexylsulfonyloxy group;

C1-C6 alkoxysulfonyloxy group: a methoxysulfonyloxy group, anethoxysulfonyloxy group, a propoxysulfonyloxy group, and ahexyloxysulfonyloxy group;

5- or 6-membered cyclic group formed with a carbon atom which is bondedto R¹⁰ and R¹¹, and R^(10-17A) and R^(11-17B), or R^(10-19A) andR^(11-19A): a cyclopentylidene group, and a cyclohexylidene group.

A compound of the formula (1-a) wherein R1 is a hydrogen atom can existas tautomers of the formula (1-a′) and the formula (1-a″). The compoundof the formula (1-a) includes all of those tautomers and a mixture oftwo or more tautomers.

Each of the compound of the formulae (4) and (5) can exist as isomers.The compounds of the formulae (4) and (5) include all of the isomers.

Then, a method of the production of the present invention will beillustrated.

Production Method 1:

wherein R¹, R², R³, R⁵, G, M, n, and V are as defined above.

A compound of the formula (I) (hereinafter referred to as Compound (1))can be prepared by reacting a compound of the formula (2) thereinafterreferred to as Compound (2)) with a compound of the formula (3)(hereinafter referred to as Compound (3)).

The reaction is usually performed in the presence of a solvent. Examplesof the solvent which can be used are water; an aromatic hydrocarbonsolvent such as benzene, chlorobenzene, toluene, and xylene; ahalogenated hydrocarbon solvent such as chloroform and dichloromethane;an alcohol solvent such as methanol, ethanol, isopropanol, n-butanol,and ethylene glycol; an ester solvent such as ethyl acetate; a ketonesolvent such as acetone, methyl ethyl ketone, and methyl isobutylketone; an ether solvent such as 1,2-dimethoxyethane, diethylene glycoldimethyl ether, polyethyleneglycol, tetrahydrofuran, and dioxane; anitrile solvent such as acetonitrile and propionitrile; an aromaticheterocycle solvent such as pyridine; a sulfoxide solvent such asdimethylsulfoxide; an amide solvent such as dimethylformamide,dimethylacetamide, and N-methylpyrrolidone; or a mixture thereof.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (2) for an economic reason.

The reaction may be performed in the presence of a catalyst. Examples ofthe catalyst include a phase transfer catalyst such as a quaternaryammonium salt such as tetrabutyl ammonium chloride, tetrabutyl ammoniumbromide, tetrabutyl ammonium iodide, benzyl tri-n-butylammonium bromide,benzyl trimethyl ammonium chloride, benzyl triethyl ammonium chloride,methyl tri-n-butyl ammonium chloride, tetraethyl ammonium chloride,tetra n-butyl ammonium chloride, benzyl trimethyl ammonium bromide,benzyl triethyl ammonium bromide, tetraethyl ammonium iodide, and benzyltrimethyl ammonium iodide; and a quaternary phosphonium salt such asn-heptyltriphenylphosphonium bromide and tetraphenylphosphonium bromide.The amount of catalyst may be catalytic amount, usually 0.01 to 10 molesto 1 mole of Compound (2).

Examples of Compound (3) include a metal hydroxide such as calciumhydroxide, lithium hydroxide, sodium hydroxide, and potassium hydroxide;a metal alkoxide such as sodium methoxide, potassium methoxide, lithiummethoxide, sodium ethoxide, and sodium n-butoxide; and a metal phenoxidesuch as sodium phenoxide. They may be used as those which arecommercially available or timely prepared or diluted with a solvent. Theamount of Compound (3) may be one or more moles to 1 mole of Compound(2), though the upper limit is not limited, the amount is usually in therange of 1 to 10 moles.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from50° c. to boiling point of the used solvent. A reaction mixture may beirradiated with microwave. The reaction time is, though it may be varieddepending on the type and amount of Compound (3), the type and amount ofsolvent, the reaction temperature and the like, usually 0.1 to 100hours, typically 0.1 to 60 hours.

In particular, the reaction can be performed by mixing a solutioncontaining Compound (2) with Compound (3) or a solution containingCompound (3). The mixing may be performed by either a method which addsCompound (3) or a solution containing Compound (3) to a solutioncontaining Compound (2), or a method which adds a solution containingCompound (2) to Compound (3) or a solution containing Compound (3), andeach of the solvents used in those solutions may be same or different.When a catalyst is added, the catalyst may be added at any stage, and itmay be added during the reaction in progress.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (1) as amain product. Compound (1) can be isolated by known procedures such aswashing, filtration, concentration, and recrystallization. The isolatedCompound (1) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Production Method 2:

wherein R², R³, R⁵, G, and n are as defined above.

Compound (2) can be prepared by reacting a compound of the formula (4)(hereinafter referred to as Compound (4)) with a base.

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene solvent such aschloroform and dichloromethane; a hydrocarbon solvent such as hexane andheptane; an alcohol solvent such as methanol, ethanol, isopropanol,n-butanol, and ethylene glycol; and ether solvent such as1,2-dimethoxyethane, diethylene glycol dimethyl ether, tetrahydrofuran,and dioxane; and ester solvent such as ethyl acetate; a ketone solventsuch as acetone, methyl ethyl ketone and methyl isobutyl ketone; anitrile solvent such as acetonitrile and propionitrile; a sulfoxidesolvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (4) for an economic reason.

The reaction may be performed in the presence of a catalyst. Examples ofthe catalyst which can be used are a phase transfer catalyst such as aquaternary ammonium salt such as tetrabutylammonium bromide,tetrabutylammonium iodide, and benzyl tri-n-butylammonium bromide; and aquaternary phosphonium salt such as n-heptyl triphenylphosphoniumbromide and tetraphenylphosphonium bromide. The amount of catalyst maybe catalystic amount, usually 0.01 to 10 moles to 1 mole of Compound(4).

Examples of the base which can be used are an organic base such aspyridine, 4-dimethylaminopyridine, triethylamine, ethyldiisopropylamine,and 1,8-diazabicyclo[5.4.0]-7-undecane; a metal amide base such aslithium diisopropylamide and sodium diisopropylamide; a metal disilazidebase such as lithium hexamethyldisilazide and potassiumhexamethyldisilazide; a metal hydroxide such as lithium hydroxide,sodium hydroxide, and potassium hydroxide; a metal hydride such assodium hydride and potassium hydride; carbonates such as sodiumcarbonate, potassium carbonate, and sodium hydrogen carbonate;phosphates such as sodium phosphate, disodium hydrogen phosphate, andsodium dihydrogen phosphate; acetates such as sodium acetate; and ametal alkoxide such as sodium methoxide and lithium methoxide; among ofthem, carbonates and metal hydroxides are preferable.

The amount of base may be catalytic amount, usually 0.01 to 10 moles,preferably 0.1 to 5 moles, more preferably 0.1 to 2 moles to 1 mole ofCompound (4).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably frommelting point of the solvent to 70° C.

The reaction times is, though it may be varied depending on the type andamount of base, the type and amount of solvent, the reaction temperatureand the like, usually 0.1 to 100 hours, typically 0.1 to 24 hours.

The reaction can be performed by mixing a solution containing Compound(4) with a base or a solution containing the base. The mixing may beperformed by either a method which adds a base or a solution containingthe base to a solution containing Compound (4), or a method which adds asolution containing Compound (4) to a base or a solution containing thebase, and each of the solvents used in those solutions may be same ordifferent.

In the reaction, a dihydropyridazinone compound of the formula (13):

wherein R², R³, R⁵, G, and n are as defined above; can be observed. Thecompound of the formula (13) is a reaction intermediate, and it may besubjected to dehydration after isolation and purification or withoutisolation.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

Compound (2) can be isolated by known procedures such as washing,filtration, concentration, and recrystallization. The isolated Compound(2) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Also, Compound (2) wherein R³ is not hydrogen can be prepared from acompound wherein R³ is hydrogen. (see Journal of American ChemicalSociety, 1945, 67, 60)

Also, Compound (2) wherein n is an integer 1 or 2 can be prepared fromCompound (2) wherein n is an integer of 0.

wherein R², R³, R⁵, and G are as defined above.

A compound of the formula (2-O1) (hereinafter referred to as Compound(2-O1)) or a compound of the formula (2-O2) (hereinafter referred to asCompound (2-O2)) can be prepared by reacting a compound of the formula(2-O0) (hereinafter referred to as Compound (2-O0) with an oxidizingagent.

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a halogenated hydrocarbon solvent such as chloroform anddichloromethane; a hydrocarbon solvent such as hexane and heptane; analcohol solvent such as methanol, ethanol, isopropanol, n-butanol, andethylene glycol; an ether solvent such as 1,2-dimethoxyethane,diethylene glycol dimethyl ether, tetrahydrofuran, and dioxane; an estersolvent such as ethyl acetate; a ketone solvent such as acetone, methylethyl ketone and methyl isobutyl ketone; a nitrile solvent such asacetonitrile and propionitrile; an amide solvent such as acetonitrileand propionitrile; an amide solvent such as dimethylformamide,dimethylacetamide, and N-methylpyrrolidone; a carboxylic acid solventsuch as formic acid and acetic acid; or a mixture thereof.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (2-O0) for an economic reason.

The reaction may be performed in the presence of a catalyst. Examples ofthe catalyst which can be used are an oxide of heavy metal such astungsten or vanadium. The amount of catalyst may be catalytic amount,usually 0.01 to 10 moles to 1 mole of Compound (2-O0).

Examples of the oxidizing agent which can be used are organic peroxidesuch as tert-butyl hydroperoxide (TBHF); inorganic peroxide such ashydrogen peroxide; and peracid such as meta-choloroperbenzoic acid(mCPBA) and peracetic acid; among of them, a meta-chloroperbenzoic acidand a hydrogen peroxide are preferable.

The amount of oxidizing agent may be, for Compound (2-O2) production,tow or more moles to 1 mole, preferably 2 to 20 moles, and for Compound(2-O1) production, one or more moles, preferably 1.0 to 1.5 moles to 1mole of Compound (2-O0).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably frommelting point of a solvent to 70° C.

The reaction time is, though it may be varied depending on the type andamount of oxidizing agent, the type and amount of solvent, the reactiontemperature and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

The reaction can be performed by mixing a solution containing Compound(2-O0) with an oxidizing agent or a solution containing the oxidizingagent. The mixing may be performed by either a method which adds anoxidizing agent or a solution containing the oxidizing agent to asolution containing Compound (2-O0), or a method which adds a solutioncontaining Compound (2-O0) to a oxidizing agent or a solution containingthe oxidizing agent, and each of the solvents used in those solutionsmay be same or different. When a catalyst is used, the catalyst may beadded at any stage, and it may be added during the reaction in progress.

In the reaction, for Compound (2-O2) production, Compound (2-O1) can beobserved. Compound (2-O1) is a reaction intermediate, and it may besubjected to oxidation after isolation and purification or withoutisolation.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

Compound (2-O1) or Compound (2-O2) can be isolated by known proceduressuch as washing, filtration, concentration, and recrystallization. Theisolated Compound (2-O1) or Compound (2-O2) can be further purified byconventional techniques such as distillation, column chromatography, andrecrystallization.

Production Method 3:

wherein R², R³, R⁵, G, n, and X¹ are as defined above.

Compound (4) can be prepared by reacting a compound of the formula (6)(hereinafter referred to as Compound (6)) with a compound of the formula(5) (hereinafter referred to as Compound (5)).

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene, chlorobenzene, toluene, and Xylene; ahalogenated hydrocarbon solvent such as dichloromethane and chloroform;and aromatic heterocycle solvent such as pyridine; a hydrocarbon solventsuch as hexane and heptane; a nitrile solvent such as acetonitrile andpropionitrile; an ether solvent such as 1,2-dimethoxyethane, diethyleneglycol dimethyl ether, tetrahydrofuran, and dioxane; and ester solventsuch as ethyl acetate; a ketone solvent such as acetone, methyl ethylketone and methyl isobutyl ketone; a sulfoxide solvent such asdimethylsulfoxide; an amide solvent such as dimethylformamide,dimethylacetamide, and N-methylpyrrolidone; or a mixture thereof; amongof them, an aromatic hydrocarbon solvent and ether solvent arepreferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (6) for an economic reason.

The amount of Compound (5) may usually be one or more moles, preferably1.0 to 3.0 moles to 1 mole of Compound (6).

The reaction may be performed in the presence of a base.

Examples of the base which can be used are an organic base such aspyridine, 4-dimethylaminopyridine, triethylamine, ethyldiisopropylamine,and 1,8-diazabicyclo[5.4.0]-7-undecene; a metal amide base such aslithium diisopropylamide and sodium diisopropylamide; a disilazide basesuch as lithium hexamethyldisilazide and potassium hexamethyldisilazide;a metal hydride such as sodium hydride and potassium hydride; a metalhydroxide such as sodium hydroxide and potassium hydroxide; carbonatessuch as sodium carbonate, potassium carbonate, and sodium hydrogencarbonate; phosphates such as sodium phosphate, disodium hydrogenphosphate, and sodium dihydrogen phosphate; acetates such as sodiumacetate; and a metal alkoxide such as sodium methoxide and lithiummethoxide; among of them, an organic base is preferable.

The amount of the base may usually be one or more moles, preferably 1 to5 moles to 1 mole of Compound (6).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from−30° C. to 50° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of base, the type and amount of solventand the like, usually 0.1 to 100 hours, typically 0.1 to 24 hours.

The reaction is performed by mixing Compound (6) or a solutioncontaining Compound (6) with a solution containing Compound (5). Themixing may be performed by either a method which adds Compound (6) or asolution containing Compound (6) to a solution containing Compound (5)at a favorable temperature, or a method which adds a solution containingCompound (5) to a solution containing Compound (6) at a favorabletemperature, preferably a method which adds a solution containingCompound (6) to a solution containing Compound (5) at a favorabletemperature. Each of the solvents used in those solutions may be same ordifferent. When a base is used, though the base may be added at anystage, preferably, a base is added to a solution containing Compound(5), and then a solution containing Compound (6) is added at a favorabletemperature.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (4) as amain product. Compound (4) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(4) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Production Method 4:

wherein R², R³, R⁵, G, and n are as defined above.

Compound (4) can be prepared by reacting a compound of the formula (7)(hereinafter referred to as Compound (7)) with a compound of the formula(12) (hereinafter referred to as Compound (12)).

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene, chlorobenzene, toluene, and xylene; ahalogenated hydrocarbon solvent such as dichloromethane and chloroform;a hydrocarbon solvent such as hexane and heptane; an alcohol solventsuch as methanol, ethanol, isopropanol, n-butanol, and ethylene glycol;an ether solvent such as 1,2-dimethoxyethane, diethylene glycol dimethylether, tetrahydrofuran, and dioxane; a nitrile solvent such asacetonitrile and propionitrile; an ester solvent such as ethyl acetate;a sulfoxide solvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof; among of them, an alcohol solvent and an aromatichydrocarbon solvent are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (12) for an economic reason.

Compound (7) can usually be purchased or timely prepared. The method forproducing Compound (7) is described, for example, in Organic Synthesis,1977, 56, 72-74 or Heterocycles, 2007, 73 469-480.

The amount of Compound (7) may usually be one or more moles, preferably1.0 to 3.0 moles to 1 mole of Compound (12).

The reaction may be performed in the presence of a dehydrating agent oran acid. Dehydration may also be achieved by azeotropic distillation.

Examples of the dehydrating agent which can be used are an inorganicdehydrating agent such as silica gel, molecular sieves, sodium sulfate,and magnesium sulfate.

The amount of dehydrating agent may usually be one or more parts byweight, preferably 1 to 5 parts by weight to 1 part by weight ofCompound (12).

Examples of the acid include an organic acid such as methanesulfonicacid, p-toluenesulfonic acid, and acetic acid; and an inorganic acidsuch as hydrochloric acid, sulfuric acid, and phosphoric acid.

The amount of acid may usually be catalytic amount, for example, 0.01 to10 moles to 1 mole of Compound (12).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 150° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of dehydrating agent or acid, the typeand amount of solvent and the like, usually 0.1 to 100 hours, typically0.1 to 24 hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (4) as amain product. Compound (4) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(4) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Compound (4) wherein R³ is not hydrogen can also be prepared from acompound wherein R³ is hydrogen. (see Journal of Organic Chemistry,1998, 63, 8145-8149)

Production Method 5:

wherein R³, G, and Y are as defined above.

Compound (12) can be prepared by reacting a compound of the formula (9)(hereinafter referred to as Compound (9)) with a compound of the formula(14) (hereinafter referred to as Compound (14)).

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a halogenated hydrocarbon solvent such as dichloromethane andchloroform; a hydrocarbon solvent such as hexane and heptane; an alcoholsolvent such as methanol, ethanol, isopropanol, n-butanol, and ethyleneglycol; an ether solvent such as 1,2-dimethoxyethane, diethylene glycoldimethyl ether, tetrahydrofuran, and dioxane; a nitrile solvent such asacetonitrile and propionitrile; an ester solvent such as ethyl acetate;a sulfoxide solvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof; among of them, an alcohol solvent is preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight of 1 part by weight of Compound (9) for an economic reason.

The amount of Compound (14) may usually be one or more moles, preferably1.0 to 3.0 moles to 1 mole of Compound (9).

Compound (14) may be purchased or timely prepared. The method forproducing Compound (14) is described, for example, in Science ofSynthesis, 40b, 1133-1210. Examples of the compound (14) are hydrazine,monomethylhydrazine, monoethylhydrazine, monomethoxycarbonylhydrazine,monobenzylhydrazine, hydrochloride or sulfate of those hydrazinecompounds. Among of them, hydrazine and methylhydrazine are preferable.

The reaction may be performed in the presence of a base.

Examples of the base which can be used are an organic base such aspyridine, 4-dimethylaminopyridine, triethylamine, ethyldiisopropylamine,and 1,8-diazabicyclo[5.4.0]-7-undecene; a metal amide base such aslithium diisopropylamide and sodium diisopropylamide; a disilazide basesuch as lithium hexamethyldisilazide and potassium hexamethyldisilazide;a metal hydride such as sodium hydride and potassium hydride; a metalhydroxide such as sodium acetate; and a metal alkoxide such as sodiummethoxide and lithium methoxide; among of them, an organic base ispreferable.

The amount of base may usually be catalytic amount, usually 0.1 to 5moles to 1 mole of Compound (14).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 50° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of base, the type and amount of solventand the like, usually 0.1 to 100 hours, typically 0.1 to 24 hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (12), orthe salt of Compound (12) when the salt of Compound (14) is used as amain product. A salt of Compound (12) can be converted to Compound (12)by basification with a base such as metal hydroxide (ex. sodiumhydroxide, potassium hydroxide) and carbonate (ex. sodium carbonate,sodium hydrogen carbonate and potassium carbonate). Compound (12) can beisolated by known procedures such as filtration, concentration, andrecrystallization. The isolated Compound (12) can be further purified byconventional techniques such as distillation, column chromatography, andrecrystallization.

Production Method 6:

wherein R², R³, R⁵, and n are as defined above.

Compound (5) can be prepared by reacting a compound of the formula (7)(hereinafter referred to as Compound (7)) with a compound of the formula(14) (hereinafter referred to as Compound (14)).

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene and chlorobenzene, toluene andxylene; a halogenated hydrocarbon solvent such as dichloromethane andchloroform; a hydrocarbon solvent such as hexane and heptane; an alcoholsolvent such as methanol, ethanol, isopropanol, n-butanol, and ethyleneglycol; an ether solvent such as 1,2-dimethoxyethane diethylene glycoldimethyl ether, tetrahydrofuran, and dioxane; a nitrile solvent such asacetonitrile and propionitrile; an ester solvent such as ethyl acetate;a sulfoxide solvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof; among of them, an alcohol solvent, an aromatichydrocarbon solvent, water, and mixed solvent of an aromatic hydrocarbonsolvent and water are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (7) for an economic reason.

Compound (14) may be purchased or timely prepared. The method forproducing Compound (14) is described, for example, in Science ofSynthesis, 40b 1133-1210. Examples of Compound (14) which can be usedare hydrazine, monomethylhydrazine, monoethylhydrazine, andmonomethoxycarbonylhydrazine, and a hydrate, hydrochloride or sulfate ofthose hydrazine compounds; among of them, hydrazine, hydrochloride ofmonobenzylhydrazine and methylhydrazine are preferable.

The amount of Compound (14) may usually be one or more moles, preferably1.0 to 3.0 moles to 1 mole of Compound (7).

The reaction may be performed in the presence of a dehydrating agent oran acid. Dehydration may also be achieved by azeotropic distillation.

Examples of the dehydrating agent which can be used are an inorganicdehydrating agent such as silica gel, molecular sieve, sodium sulfate,and magnesium sulfate.

The amount of dehydrating agent may usually be one or more parts byweight, preferably 1 to 5 parts by weight, to 1 part by weight ofCompound (7).

Examples of the acid which can be used are an organic acid such asmethanesulfonic acid, p-toluenesulfonic acid and acetic acid; and aninorganic acid such as hydrochloric acid, sulfuric acid, and phosphoricacid.

The amount of acid may usually be catalytic amount, usually 0.01 to 10moles to 1 mole of Compound (7).

Compound (7) may usually be purchased or timely prepared. The method forproducing Compound (7) is described, for example, in Organic Synthesis,1977, 56, 72-74 or Heterocycles, 2007, 73 469-480.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 50° C.

The reaction time is, though it may be varied depending on the reactiontemperatures, the type and amount of base, the type and amount ofsolvent and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (5), orsalt of Compound (5) when salt of Compound (14) is used as a mainproduct. A salt of Compound (5) can be converted to Compound (5) bybasification with a base such as metal hydroxide (ex. sodium hydroxide,potassium hydroxide) and carbonate (ex. sodium carbonate, sodiumhydrogen carbonate and potassium carbonate). Compound (5) can beisolated by known procedures such as filtration, concentration, andrecrystallization. The isolated Compound (5) can be further purified byconventional techniques such as distillation, column chromatography, andrecrystallization.

Production Method 7:

wherein G and X¹ are as defined above.

Compound (6) can be prepared by halogenation of a compound of theformula (8) (hereinafter referred to as Compound (8)) with ahalogenating agent.

A solvent may be used in the reaction.

Examples of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene chlorobenzene, toluene, and xylene; ahalogenated hydrocarbon solvent such as dichloromethane and chloroform;a hydrocarbon solvent such as hexane and heptane; an ether solvent suchas 1,2-dimethoxyethane, diethylene glycol dimethyl ether,tetrahydrofuran, and dioxane; or a mixture thereof; among of them, anaromatic hydrocarbon solvent is preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (8) for an economic reason.

Examples of the halogenating agent are thionyl chloride, thionylbromide, phosphorous oxychloride, and oxalyl chloride; among of them,thionyl chloride is preferable.

The amount of halogenating agent may be one or more moles to 1 mole ofCompound (8). Though the upper limit is not limited, the amount isusually in the range of 1 to 10 moles.

The reaction can be performed in the presence of a catalyst.

Example of the catalyst which can be used is an amide compound such asdimethylformamide, among of them, dimethylformamide is preferable.

The amount of the catalyst may be 0.01 or more moles to 1 mole ofCompound (8). Though the upper limit is not limited, the amount isusually in the range of 0.01 to 0.5 moles.

The reaction temperature is usually not less than 35° C. and not morethan boiling point of the solvent, preferably from 40° C. to 100° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of halogenating agent, the type andamount of solvent, presence or absence of a catalyst and the like,usually 0.1 to 100 hours, typically 0.1 to 24 hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography, andNMR can be used. The reaction mixture thus obtained usually containsCompound (6) as a main product. Compound (6) can be isolated by knownprocedures such as washing, filtration, concentration, andrecrystallization. The isolated Compound (6) can be further purified byconventional techniques such as distillation, column chromatography, andrecrystallization.

Also, Compound (6) can be prepared by using Friedel-Crafts acylation asshown in the following scheme:

wherein G and X¹ are as defined above.(see European J of Organic Chemistry, 2002, 14, 2298-2307)Production Method 8:

wherein G, and Y are as defined above.

Compound (8) can be prepared by hydrolysis of a compound of the formula(9) (hereinafter referred to as Compound (9)).

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a halogenated hydrocarbon solvent such as dichloromethane andchloroform; an alcohol solvent such as methanol, ethanol, isopropanol,n-butanol, and ethylene glycol dimethyl ether; an ether solvent such as1,2-dimethoxyethane, diethylene glycol, tetrahydrofuran, and dioxane; anitrile solvent such as acetonitrile and propionitrile; a sulfoxidesolvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof; among of them, water, an ether solvent such astetrahydrofuran, an alcohol solvent such as methanol or an aromatichydrocarbon solvent such as toluene and xylene; or a mixture thereof arepreferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (9) for an economic reason.

The reaction can be performed in the presence of a base.

Examples of the base which can be used are a metal hydroxide such assodium hydroxide, potassium hydroxide, and lithium hydroxide.

The amount of the base may be one or more moles to 1 mole of Compound(9). Though the upper limit is not limited, the amount is usually 1 to10 moles.

The reaction can be performed in the presence of an acid in place of abase.

Examples of the acid which can be used are an inorganic acid such ashydrochloric acid, sulfuric acid, acetic acid, and phosphoric acid.

The amount of the acid may be a catalytic amount. Though the upper limitis not limited, the amount is usually in the range of 0.01 to 10 molesto 1 mole of Compound (9).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably fromroom temperature to boiling point of a solvent.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of a base or acid, the type and amountof solvent and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (8) or asalt of Compound (8), when a base was used, as a main product. A salt ofCompound (8) can be converted to Compound (8) by acidification with anacid such as hydrochloric acid and sulfuric acid. Compound (8) can beisolated by known procedures such as washing, filtration, concentration,and recrystallization. The isolated Compound (8) can be further purifiedby conventional techniques such as distillation, recrystallization andcolumn chromatography.

Production Method 9:

wherein G, X², and Y are as defined above.

Compound (9) can be prepared by reacting a Grignard reagent which isprepared from a compound of the formula (10) (hereinafter referred to asCompound (10)) with a compound of the formula (15) (hereinafter referredto as Compound (15)):

wherein Y is as defined above.

Examples of Compound (10) which can be used are a halogenated benzenesuch as bromobenzene, chlorobenzene, iodobenzene, 2-methylbromobenzene,3-methylbromobenzene, 4-methylbromobenzene, 2,4-dimethylbromobenzene,2,4,6-trimethylbromobenzene, 2,3,5-trimethylbromobenzene,2,4,6-triethylbromobenzene, 2,4,6-tributylbromobenzene,2-bromo-4-(4-chlorophenyl)-1-ethylbenzene, and2,6-diethyl-4-methylbromobenzene; a halogenated naphthalene such as1-bromonaphthalene and 2-bromonaphthalene; a halogenated furan such as3-bromofuran; a halogenated pyridine such as 2-bromopyridine,3-bromopyridine, and 4-bromopyridine; a halogenated pyrimidine such as2-bromopyrimidine and 4-bromopyrimidine; a halogenated quinoline such as3-bromoquinoline, 4-bromoquinoline, 6-bromoquinoline, and8-bromoquinoline; a halogenated thiophene such as 2-bromothiophene,3-bromothiophene, and 4-bromothiophene; a halogenated thiazole such as2-bromothiazole, 4-bromothiazole, and 5-bromothiazole; and a halogenatedthianaphthalene such as 3-bromothianaphthalene; among of them, ahalogenated benzene is preferable, and a brominated benzene and aniodinated benzene are more preferable. They may be purchases or timelyprepared. The method for producing Compound (10) is described, forexample, in Jikken Kaguku Kouza 19, Organic synthesis I, Hydrocarbon andHalide, fourth edition, 363-479, Maruzen Co., 1991.

The reaction comprises the first step of preparing Grignard reagent fromCompound (10) and the second step of reacting Grignard reagent withCompound (15).

First Step:

The reaction is usually performed in the presence of a solvent.

Example of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene toluene, and xylene; a hydrocarbon solvent suchas hexane and heptane; an ether solvent such as 1,2-dimethoxyethane,diethylene glycol dimethyl ether, tetrahydrofuran, and dioxane; or amixture thereof; among of them, an ether solvent is preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (10) for an economic reason.

The type of magnesium used in the present invention is not limited, butcutting chip form is favorable for a safety and availability reason.

The amount of magnesium may be one or more moles to 1 mole of Compound(10). Though the upper limit is not limited, the amount is usually inthe range of 1 to 2 moles. An activating agent such as dibromoethane andiodine may be added because commercial magnesium has usually oxidelayer, thereby the reactivity is reduced.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 50° C. The reaction time is, though it may be varied dependingon the reaction temperature, the form and amount of magnesium, the typeand amount of solvent, presence or absence of an activating agent andthe like, usually 0.1 to 100 hours, typically 0.1 to 24 hours.

Second Step:

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene toluene, and xylene; a hydrocarbon solvent suchas hexane and heptane; an ether solvent such as 1,2-dimethoxyethane,diethylene glycol dimethyl ether, tetrahydrofuran, and dioxane; or amixture thereof; among of them, an ether solvent and an aromatichydrocarbon solvent; or a mixture thereof are preferable.

The solvent may be same as or different from the solvent used in thefirst step.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (10) for an economic reason.

Examples of Compound (15) which can be used are oxalates which thenumber of carbon in the ester moiety is 1-6 such as dimethyl oxalate,diethyl oxalate, dipropyl oxalate, dibutyl oxalate, dipentyl oxalate,and dihexyl oxalate; among of them, a diethyl oxalate is preferable.

The amount of Compound (15) may be one or more moles to 1 mole ofCompound (10). Though the upper limit is not limited, the amount isusually in the range of 1 to 3 moles.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 30° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of Compound (15), the type and amountof solvent and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

The reaction is performed by mixing a solution from the first step withCompound (15) or a solution of Compound (15). The mixing may beperformed by either a method wherein a solution from the first step at afavorable temperature, then a solution containing Compound (15) is addedthereto; or a method wherein a solution from the first step is addeddropwise to a solution containing Compound (15) at a favorabletemperature.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (9) as amain product. Compound (9) can be isolated by known procedures such aswashing, filtration, concentration, and recrystallization. The isolatedCompound (9) can be further purified by conventional techniques such asdistillation, and column chromatography, (see Journal of OrganicChemistry, 1987, 52, 5026-5030)

Compound (9) can be prepared from Compound (16) by reacting a compoundwhich is prepared by metalation reaction using an alkyl lithium basesuch as n-butyl lithium and tert-butyl lithium or a metal amide basesuch as lithium diisopropylamide with an oxalate diester as shown in thefollowing scheme:

wherein X³ represents a hydrogen atom, and G and Y are as defined above.Production Method 10:

wherein R¹⁰, R¹¹ and G^(B) are as defined above.

A compound of the formula (17) (hereinafter referred to as Compound(17)) can be prepared by reacting a compound of the formula (12B)(hereinafter referred to as Compound (12B)) with a compound of theformula (20) (hereinafter referred to as Compound (20))

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are an aromatic hydrocarbonsolvent such as benzene, chlorobenzene, toluene, and xylene; ahalogenated hydrocarbon solvent such as dichloromethane and chloroform;a hydrocarbon solvent such as hexane and heptane; an alcohol solventsuch as methanol, ethanol, isopropanol, n-butanol, and ethylene glycoldimethyl ether; an ether solvent such as 1,2-dimethoxyethane, diethyleneglycol dimethyl ether, tetrahydrofuran, and dioxane; a nitrile solventsuch as acetonitrile and propionitrile; a ester solvent such as ethylacetate; a sulfoxide solvent such as dimethylsulfoxide; an amido solventsuch as dimethylformamide, dimethylacetamide, and N-methylpyrrolidone;or a mixture thereof; among of them, an alcohol solvent and an aromatichydrocarbon solvent are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (12B) for an economic reason.

The compound (20) can be purchased. Examples of the compound (20) areformaldehyde, acetaldehyde, propanal, butanal, isobutanal, benzaldehyde,acetone, methyl ethyl ketone, methyl isobutyl ketone, acetophnone,cyclopentanone, and cyclohexanone.

The amount of the compound (20) may be one or more moles, preferably 1.0to 3.0 moles to 1 mole of Compound (12B).

The reaction may be performed in the presence of a dehydrating agent oran acid. Dehydration may also be achieved by azeotropic distillation.

Examples of the dehydrating agent are inorganic dehydrating agent suchas silica gel, molecular sieves, sodium sulfate and magnesium sulfate.

The amount of the dehydrating agent may be one or more parts by weight,preferably 1 to 5 parts by weight to 1 part by weight of Compound (12B).

Examples of the acid are an organic acid such as methanesulfonic acid,p-toluenesulfonic acid and acetic acid, and an inorganic acid such ashydrochloric acid, sulfuric acid and phosphoric acid.

The amount of the acid is 0.01 to 10 moles to 1 mole of Compound (12B).The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably from0° C. to 150° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of the dehydrating agent or the acid,the type and amount of solvent and the like, usually 0.1 to 100 hours,typically 0.1 to 24 hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (12) as amain product. Compound (17) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(17) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Production Method 11:

wherein R^(3B), R¹⁰, R¹¹, L and G^(B) are as defined above.

A compound of the formula (19) (hereinafter referred to as Compound(19)) can be prepared by reacting Compound (17) with a compound of theformula (18) (hereinafter referred to as Compound (18)).

Examples of the compound (18) are methyl iodide, ethyl bromide, benzylchloride, methyl methanesulfonate dimethylsulfate, and diethylsulfate.They may be purchased or timely prepared.

The reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a halogenated hydrocarbon solvent such as dichloromethane andchloroform; a hydrocarbon solvent such as hexane and heptane; a nitrilesolvent such as acetonitrile and propionitrile; an ether solvent such as1,2-dimethoxyethane, diethylene glycol dimethyl ether, tetrahydrofuran,and dioxane; an ester solvent such as ethyl acetate; a ketone solventsuch as acetone, methyl ethyl ketone and methyl isobutyl ketone; asulfoxide solvent such as dimethylsulfoxide; an amide solvent such asdimethylformamide, dimethylacetamide, and N-methylpyrrolidone; or amixture thereof; among of them, a ketone solvent and an aromatichydrocarbon solvent are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (17) for an economic reason.

The amount of Compound (18) may usually be one or more moles, preferably1.0 to 3.0 moles to 1 mole of Compound (17).

The reaction may be performed in the presence of a base.

Examples of the base which can be used are an organic base such aspyridine, 4-dimethylaminopyridine, triethylamine, ethyldiisopropylamine,and 1,8-diazabicyclo[5.4.0]-7-undecene; a metal hydride such as sodiumhydride and potassium hydride; a metal hydroxide such as lithiumhydroxide, sodium hydroxide and potassium hydroxide; a carbonate such assodium carbonate, potassium carbonate and sodium hydrogen carbonate; aphosphate such as sodium phosphate, disodium hydrogen phosphate andsodium dihydrogen phosphate; an acetate such as sodium acetate; and ametal alkoxide such as sodium methoxide and lithium methoxide; among ofthem, a metal hydroxide and a carbonate are preferable.

The amount of base may be one or more moles, usually 1 to 5 moles to 1mole of Compound (17).

The reaction may be performed in the presence of a catalyst.

Examples of the catalyst include a phase transfer catalyst such as aquaternary ammonium salt such as tetrabutyl ammonium bromide, tetrabutylammonium iodide and benzyl tri-n-butylammonium bromide, and a quaternaryphosphonium salt such as n-heptyltriphenylphosphonium bromide andtetraphenylphosphonium bromide; and a hydrazine such as hydrazinehydrate, methyl hydrazine and N, N-dimethylhydrazine.

The amount of catalyst may be catalytic amount, usually 0.01 to 1 molesto 1 mole of Compound (17).

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably −30°C. to 50° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of base, the type and amount ofsolvent, and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (19) as amain product. Compound (19) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(19) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Production Method 12:

wherein R^(2B), R¹⁰, R¹¹ and G^(B) are as defined above.

A compound of the formula (12C) (hereinafter referred to as Compound(12C)) can be prepared by decomposing Compound (19).

Examples of the method of the decomposition are hydrolysis andhydrogenation.

A hydrolysis reaction is usually performed in the presence of a solvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a halogenated hydrocarbon solvent such as dichloromethane andchloroform; a hydrocarbon solvent such as hexane and heptane; an alcoholsolvent such as methanol, ethanol, isopropanol, n-butanol and ethyleneglycol; an ether solvent such as 1,2-dimethoxyethane, diethylene glycoldimethyl ether, tetrahydrofuran and dioxane; a nitrile solvent such asacetonitrile and propionitrile; a sulfoxide solvent such asdimethylsulfoxide; an amide solvent such as dimethylformamide,dimethylacetamide, and N-methylpyrrolidone; or a mixture thereof; amongof them, water, an alcohol solvent, an ether solvent and a mixturethereof are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (19) for an economic reason.

The reaction may be performed in the presence of an acid.

Examples of the acid are an organic acid such as methanesulfonic acid,p-toluenesulfonic acid and acetic acid; and an inorganic acid such ashydrochloric acid, sulfuric acid and phosphoric acid.

The amount of the acid may be usually a catalytic amount, and 0.01 to 1mole to 1 mole of Compound (19).

This reaction may be performed in the presence of a hydroxylamine; or ahydrochloride, a sulfate or a carbonate thereof.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably 0° C.to 150° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of acid, the type and amount ofsolvent, and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (12C) as amain product. Compound (12C) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(12C) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

When at least one of R¹⁰ and R¹¹ is a phenyl group, a hydrogenationreaction can be performed.

A hydrogenation reaction is usually performed in the presence of asolvent.

Examples of the solvent which can be used are water; an aromatichydrocarbon solvent such as benzene, chlorobenzene, toluene, and xylene;a hydrocarbon solvent such as hexane and heptane; an alcohol solventsuch as methanol, ethanol, isopropanol, n-butanol and ethylene glycol;an ether solvent such as 1,2-dimethoxyethane, diethylene glycol dimethylether, tetrahydrofuran and dioxane; an ester solvent such as ethylacetate; or a mixture thereof; among of them, water, an alcohol solvent,an ether solvent and a mixture thereof are preferable.

The amount of solvent is not limited, but usually 100 or less parts byweight to 1 part by weight of Compound (19) for an economic reason.

The reaction may be usually performed in the presence of a catalyst.

Examples of the catalyst are those which metal such as palladium,platinum and rhodium is supported on activated carbon.

The rate of metal to activated carbon is not limited, but usually 0.1 to10% by weight to 100% by weight activated carbon.

The amount of catalyst may be catalytic amount, and 0.001 to 0.1 part byweight to 1 part by weight of compound (19).

The reaction pressure is usually not less than atmosphere pressure andnot more than 10 atm.

The reaction temperature is usually not less than melting point of asolvent and not more than boiling point of the solvent, preferably 0° C.to 80° C.

The reaction time is, though it may be varied depending on the reactiontemperature, the type and amount of catalyst, the type and amount ofsolvent, and the like, usually 0.1 to 100 hours, typically 0.1 to 24hours.

In order to monitor the progress of the reaction, conventional analysistechniques such as thin layer chromatography, gas chromatography,high-performance liquid chromatography, and NMR can be used.

The reaction mixture thus obtained usually contains Compound (12C) as amain product. Compound (12C) can be isolated by known procedures such asfiltration, concentration, and recrystallization. The isolated Compound(12C) can be further purified by conventional techniques such asdistillation, column chromatography, and recrystallization.

Examples of the compound which can be prepared by the method ofproducing of the present invention include as follows.

The combination of the symbols in the formula (1-1) to formula (1-31),formula (2-1) to formula (2-72), and formula (4-1_ to formula (4-72) isshown in Tables 1-24. The combination of the symbols in the formula(1-101) to formula (1-115), formula (2-101) to formula (2-146), formula(4-101) to formula (4-145) is shown in Tables 25-26. The combination ofthe symbols in the formula (12-1) to formula (12-8) is shown in Tables27-29, formula (1-201) and formula (1-301) is shown in Tables 30-31, andformula (2-201) to formula (2-203), formula (4-201) to formula (4-203),formula (2-301) to formula (2-303) and formula (4-301) to formula(4-303) is shown in Tables 32-37. The combination of the symbols in theformula (40-a) is shown in Table 38, the combination of symbols in theformula (40-b) is shown in Table 39, and the combination of the symbolsin the formula (41-a) is shown in Table 40.

In the formulae and tables, “Me” means a methyl group, “Et” means anethyl group, “n-Pr” means a n-propyl group, “i-Pr” means an isopropylgroup, “c-Pr” means a cyclopropyl group, “n-Bu” means a n-butyl group,and “Ph” means a phenyl group.

TABLE 1 No. R3 Z1 (Z2)m (1)-1 Me Me 4-Me (1)-2 Me Me 6-Me (1)-3 Me Me4-Me, 6-Me (1)-4 Me Me 4-Me, 6-Cl (1)-5 Me Me 4-Cl (1)-6 Me Me 4-Cl,6-Me (1)-7 Me Me 4-Cl, 6-Br (1)-8 Me Me 3-Br, 6-Me (1)-9 Me Me 4-Br,6-Br (1)-10 Me Me 4-F, 6-F (1)-11 Me Me 3-(4-Cl—Ph) (1)-12 Me Me 5-Ph(1)-13 Me Me 5-(2-Cl—Ph) (1)-14 Me Me 5-(2-Br—Ph) (1)-15 Me Me5-(2-F—Ph) (1)-16 Me Me 5-(2-OMe—Ph) (1)-17 Me Me 5-(2-Me—Ph) (1)-18 MeMe 5-(2-CF3—Ph) (1)-19 Me Me 5-(3-Cl—Ph) (1)-20 Me Me 5-(3-Br—Ph) (1)-21Me Me 5-(3-F—Ph) (1)-22 Me Me 5-(3-OMe—Ph) (1)-23 Me Me 5-(3-Me—Ph)(1)-24 Me Me 5-(3-CF3—Ph) (1)-25 Me Me 5-(4-Cl—Ph) (1)-26 Me Me5-(4-Br—Ph) (1)-27 Me Me 5-(4-F—Ph) (1)-28 Me Me 5-(4-OMe—Ph) (1)-29 MeMe 5-(4-Me—Ph) (1)-30 Me Me 5-(4-CF3—Ph) (1)-31 Me CF3 5-CF3 (1)-32 MeEt — (1)-33 Me Et 4-Me (1)-34 Me Et 6-Me (1)-35 Me Et 4-Me, 6-Me (1)-36Me Et 4-Me, 6-OMe (1)-37 Me Et 4-Et (1)-38 Me Et 6-Et (1)-39 Me Et 4-Me,6-Et (1)-40 Me Et 4-Et, 6-Et

TABLE 2 No. R3 Z1 (Z2)m (1)-41 Me Et 4-C≡CH, 6-Et (1)-42 Me Et 4-c-Pr,6-Et (1)-43 Me Et 4-Ph, 6-Et (1)-44 Me Et 4-Ph, 6-C≡CH (1)-45 Me Et4-Ph, 6-OMe (1)-46 Me Et 4-(4-Me—Ph), 6-Et (1)-47 Me Et 4-(4-Cl—Ph),6-Et (1)-48 Me Et 4-CN, 6-Et (1)-49 Me Et 4-OMe, 6-Et (1)-50 Me Et4-NO2, 6-Et (1)-51 Me Et 4-Cl, 6-Et (1)-52 Me Et 4-Br, 6-Et (1)-53 Me Et4-F, 6-Et (1)-54 Me Et 5-Ph (1)-55 Me Et 5-(2-Cl—Ph) (1)-56 Me Et5-(2-Br—Ph) (1)-57 Me Et 5-(2-F—Ph) (1)-58 Me Et 5-(2-OMe—Ph) (1)-59 MeEt 5-(2-Me—Ph) (1)-60 Me Et 5-(2-CF3—Ph) (1)-61 Me Et 5-(3-Cl—Ph) (1)-62Me Et 5-(3-Br—Ph) (1)-63 Me Et 5-(3-F—Ph) (1)-64 Me Et 5-(3-OMe—Ph)(1)-65 Me Et 5-(3-Me—Ph) (1)-66 Me Et 5-(3-CF3—Ph) (1)-67 Me Et5-(4-Cl—Ph) (1)-68 Me Et 5-(4-Br—Ph) (1)-69 Me Et 5-(4-F—Ph) (1)-70 MeEt 5-(4-OMe—Ph) (1)-71 Me Et 5-(4-Me—Ph) (1)-72 Me Et 5-(4-CF3—Ph)(1)-73 Me n-Pr — (1)-74 Me c-Pr 4-Me, 6-Et (1)-75 Me C≡CH 4-Me, 6-Me(1)-76 Me CN 4-Me, 6-Me (1)-77 Me CN 4-Me, 6-Et (1)-78 Me OMe 4-Me, 6-Me(1)-79 Me OEt 3-F, 6-F (1)-80 Me NO2 —

TABLE 3 No. R3 Z1 (Z2)m (1)-81 Me F 3-F (1)-82 Me F 5-F (1)-83 Me F 6-F(1)-84 Me F 3-Me, 6-F (1)-85 Me F 3-OMe, 6-F (1)-86 Me F 3-OEt, 6-F(1)-87 Me F 3-F, 5-Cl (1)-88 Me F 3-F, 6-F (1)-89 Me Cl — (1)-90 Me Cl6-Me (1)-91 Me Cl 6-CF3 (1)-92 Me Cl 5-Ph (1)-93 Me Cl 3-Cl (1)-94 Me Cl4-Cl (1)-95 Me Cl 6-Cl (1)-96 Me Cl 4-Br (1)-97 Me Cl 6-Br (1)-98 Me Cl4-F (1)-99 Me Cl 6-F (1)-100 Me Cl 4-Me, 6-F (1)-101 Me Cl 4-Me, 6-Cl(1)-102 Me Cl 4-Me, 6-Br (1)-103 Me Cl 4-Me, 6-F (1)-104 Me Cl 4-Me,6-OCF3 (1)-105 Me Cl 4-Me, 6-c-Pr (1)-106 Me Cl 4-OCF3, 6-Cl (1)-107 MeCl 4-Cl, 6-Me (1)-108 Me Cl 4-Cl, 6-Et (1)-109 Me Cl 4-Cl, 6-c-Pr(1)-110 Me Cl 4-Cl, 6-OCF3 (1)-111 Me Cl 4-Cl, 6-Br (1)-112 Me Cl 4-Br,6-Br (1)-113 Me Cl 4-Br, 6-OCF3 (1)-114 Me Cl 4-F, 6-F (1)-115 Me Cl4-OMe, 6-Et (1)-116 Me Br 4-Me, 6-Me (1)-117 Me Br 4-Me, 6-Et (1)-118 MeBr 4-Me, 6-Br (1)-119 Me Br 4-Cl, 6-OCF3 (1)-120 Me Br 4-Br, 6-OCF3

TABLE 4 No R3 Z1 (Z2)m (2)-1 Et Me 4-Me (2)-2 Et Me 6-Me (2)-3 Et Me4-Me, 6-Me (2)-4 Et Me 4-Me, 6-Cl (2)-5 Et Me 4-Cl (2)-6 Et Me 4-Cl,6-Me (2)-7 Et Me 4-Cl, 6-Br (2)-8 Et Me 3-Br, 6-Me (2)-9 Et Me 4-Br,6-Br (2)-10 Et Me 4-F, 6-F (2)-11 Et Me 3-(4-Cl—Ph) (2)-12 Et Me 5-Ph(2)-13 Et Me 5-(2-Cl—Ph) (2)-14 Et Me 5-(2-Br—Ph) (2)-15 Et Me5-(2-F—Ph) (2)-16 Et Me 5-(2-OMe—Ph) (2)-17 Et Me 5-(2-Me—Ph) (2)-18 EtMe 5-(2-CF3—Ph) (2)-19 Et Me 5-(3-Cl—Ph) (2)-20 Et Me 5-(3-Br—Ph) (2)-21Et Me 5-(3-F—Ph) (2)-22 Et Me 5-(3-OMe—Ph) (2)-23 Et Me 5-(3-Me—Ph)(2)-24 Et Me 5-(3-CF3—Ph) (2)-25 Et Me 5-(4-Cl—Ph) (2)-26 Et Me5-(4-Br—Ph) (2)-27 Et Me 5-(4-F—Ph) (2)-28 Et Me 5-(4-OMe—Ph) (2)-29 EtMe 5-(4-Me—Ph) (2)-30 Et Me 5-(4-CF3—Ph) (2)-31 Et CF3 5-CF3 (2)-32 EtEt — (2)-33 Et Et 4-Me (2)-34 Et Et 6-Me (2)-35 Et Et 4-Me, 6-Me (2)-36Et Et 4-Me, 6-OMe (2)-37 Et Et 4-Et (2)-38 Et Et 6-Et (2)-39 Et Et 4-Me,6-Et (2)-40 Et Et 4-Et, 6-Et

TABLE 5 No R3 Z1 (Z2)m (2)-41 Et Et 4-C≡CH, 6-Et (2)-42 Et Et 4-c-Pr,6-Et (2)-43 Et Et 4-Ph, 6-Et (2)-44 Et Et 4-Ph, 6-C≡CH (2)-45 Et Et4-Ph, 6-OMe (2)-46 Et Et 4-(4-Me—Ph), 6-Et (2)-47 Et Et 4-(4-Cl—Ph),6-Et (2)-48 Et Et 4-CN, 6-Et (2)-49 Et Et 4-OMe, 6-Et (2)-50 Et Et4-NO2, 6-Et (2)-51 Et Et 4-Cl, 6-Et (2)-52 Et Et 4-Br, 6-Et (2)-53 Et Et4-F, 6-Et (2)-54 Et Et 5-Ph (2)-55 Et Et 5-(2-Cl—Ph) (2)-56 Et Et5-(2-Br—Ph) (2)-57 Et Et 5-(2-F—Ph) (2)-58 Et Et 5-(2-OMe—Ph) (2)-59 EtEt 5-(2-Me—Ph) (2)-60 Et Et 5-(2-CF3—Ph) (2)-61 Et Et 5-(3-Cl—Ph) (2)-62Et Et 5-(3-Br—Ph) (2)-63 Et Et 5-(3-F—Ph) (2)-64 Et Et 5-(3-OMe—Ph)(2)-65 Et Et 5-(3-Me—Ph) (2)-66 Et Et 5-(3-CF3—Ph) (2)-67 Et Et5-(4-Cl—Ph) (2)-68 Et Et 5-(4-Br—Ph) (2)-69 Et Et 5-(4-F—Ph) (2)-70 EtEt 5-(4-OMe—Ph) (2)-71 Et Et 5-(4-Me—Ph) (2)-72 Et Et 5-(4-CF3—Ph)(2)-73 Et n-Pr — (2)-74 Et c-Pr 4-Me, 6-Et (2)-75 Et C≡CH 4-Me, 6-Me(2)-76 Et CN 4-Me, 6-Me (2)-77 Et CN 4-Me, 6-Et (2)-78 Et OMe 4-Me, 6-Me(2)-79 Et OEt 3-F, 6-F (2)-80 Et NO2 —

TABLE 6 No R3 Z1 (Z2)m (2)-81 Et F 3-F (2)-82 Et F 5-F (2)-83 Et F 6-F(2)-84 Et F 3-Me, 6-F (2)-85 Et F 3-OMe, 6-F (2)-86 Et F 3-OEt, 6-F(2)-87 Et F 3-F, 5-Cl (2)-88 Et F 3-F, 6-F (2)-89 Et Cl — (2)-90 Et Cl6-Me (2)-91 Et Cl 6-CF3 (2)-92 Et Cl 5-Ph (2)-93 Et Cl 3-Cl (2)-94 Et Cl4-Cl (2)-95 Et Cl 6-Cl (2)-96 Et Cl 4-Br (2)-97 Et Cl 6-Br (2)-98 Et Cl4-F (2)-99 Et Cl 6-F (2)-100 Et Cl 4-Me, 6-F (2)-101 Et Cl 4-Me, 6-Cl(2)-102 Et Cl 4-Me, 6-Br (2)-103 Et Cl 4-Me, 6-F (2)-104 Et Cl 4-Me,6-OCF3 (2)-105 Et Cl 4-Me, 6-c-Pr (2)-106 Et Cl 4-OCF3, 6-Cl (2)-107 EtCl 4-Cl, 6-Me (2)-108 Et Cl 4-Cl, 6-Et (2)-109 Et Cl 4-Cl, 6-c-Pr(2)-110 Et Cl 4-Cl, 6-OCF3 (2)-111 Et Cl 4-Cl, 6-Br (2)-112 Et Cl 4-Br,6-Br (2)-113 Et Cl 4-Br, 6-OCF3 (2)-114 Et Cl 4-F, 6-F (2)-115 Et Cl4-OMe, 6-Et (2)-116 Et Br 4-Me, 6-Me (2)-117 Et Br 4-Me, 6-Et (2)-118 EtBr 4-Me, 6-Br (2)-119 Et Br 4-Cl, 6-OCF3 (2)-120 Et Br 4-Br, 6-OCF3

TABLE 7 No R3 Z1 (Z2)m (3)-1 n-Pr Me 4-Me (3)-2 n-Pr Me 6-Me (3)-3 n-PrMe 4-Me, 6-Me (3)-4 n-Pr Me 4-Me, 6-Cl (3)-5 n-Pr Me 4-Cl (3)-6 n-Pr Me4-Cl, 6-Me (3)-7 n-Pr Me 4-Cl, 6-Br (3)-8 n-Pr Me 3-Br, 6-Me (3)-9 n-PrMe 4-Br, 6-Br (3)-10 n-Pr Me 4-F, 6-F (3)-11 n-Pr Me 3-(4-Cl—Ph) (3)-12n-Pr Me 5-Ph (3)-13 n-Pr Me 5-(2-Cl—Ph) (3)-14 n-Pr Me 5-(2-Br—Ph)(3)-15 n-Pr Me 5-(2-F—Ph) (3)-16 n-Pr Me 5-(2-OMe—Ph) (3)-17 n-Pr Me5-(2-Me—Ph) (3)-18 n-Pr Me 5-(2-CF3—Ph) (3)-19 n-Pr Me 5-(3-Cl—Ph)(3)-20 n-Pr Me 5-(3-Br—Ph) (3)-21 n-Pr Me 5-(3-F—Ph) (3)-22 n-Pr Me5-(3-OMe—Ph) (3)-23 n-Pr Me 5-(3-Me—Ph) (3)-24 n-Pr Me 5-(3-CF3—Ph)(3)-25 n-Pr Me 5-(4-Cl—Ph) (3)-26 n-Pr Me 5-(4-Br—Ph) (3)-27 n-Pr Me5-(4-F—Ph) (3)-28 n-Pr Me 5-(4-OMe—Ph) (3)-29 n-Pr Me 5-(4-Me—Ph) (3)-30n-Pr Me 5-(4-CF3—Ph) (3)-31 n-Pr CF3 5-CF3 (3)-32 n-Pr Et — (3)-33 n-PrEt 4-Me (3)-34 n-Pr Et 6-Me (3)-35 n-Pr Et 4-Me, 6-Me (3)-36 n-Pr Et4-Me, 6-OMe (3)-37 n-Pr Et 4-Et (3)-38 n-Pr Et 6-Et (3)-39 n-Pr Et 4-Me,6-Et (3)-40 n-Pr Et 4-Et, 6-Et

TABLE 8 No R3 Z1 (Z2)m (3)-41 n-Pr Et 4-C≡CH, 6-Et (3)-42 n-Pr Et4-c-Pr, 6-Et (3)-43 n-Pr Et 4-Ph, 6-Et (3)-44 n-Pr Et 4-Ph, 6-C≡CH(3)-45 n-Pr Et 4-Ph, 6-OMe (3)-46 n-Pr Et 4-(4-Me—Ph), 6-Et (3)-47 n-PrEt 4-(4-Cl—Ph), 6-Et (3)-48 n-Pr Et 4-CN, 6-Et (3)-49 n-Pr Et 4-OMe,6-Et (3)-50 n-Pr Et 4-NO2, 6-Et (3)-51 n-Pr Et 4-Cl, 6-Et (3)-52 n-Pr Et4-Br, 6-Et (3)-53 n-Pr Et 4-F, 6-Et (3)-54 n-Pr Et 5-Ph (3)-55 n-Pr Et5-(2-Cl—Ph) (3)-56 n-Pr Et 5-(2-Br—Ph) (3)-57 n-Pr Et 5-(2-F—Ph) (3)-58n-Pr Et 5-(2-OMe—Ph) (3)-59 n-Pr Et 5-(2-Me—Ph) (3)-60 n-Pr Et5-(2-CF3—Ph) (3)-61 n-Pr Et 5-(3-Cl—Ph) (3)-62 n-Pr Et 5-(3-Br—Ph)(3)-63 n-Pr Et 5-(3-F—Ph) (3)-64 n-Pr Et 5-(3-OMe—Ph) (3)-65 n-Pr Et5-(3-Me—Ph) (3)-66 n-Pr Et 5-(3-CF3—Ph) (3)-67 n-Pr Et 5-(4-Cl—Ph)(3)-68 n-Pr Et 5-(4-Br—Ph) (3)-69 n-Pr Et 5-(4-F—Ph) (3)-70 n-Pr Et5-(4-OMe—Ph) (3)-71 n-Pr Et 5-(4-Me—Ph) (3)-72 n-Pr Et 5-(4-CF3—Ph)(3)-73 n-Pr n-Pr — (3)-74 n-Pr c-Pr 4-Me, 6-Et (3)-75 n-Pr C≡CH 4-Me,6-Me (3)-76 n-Pr CN 4-Me, 6-Me (3)-77 n-Pr CN 4-Me, 6-Et (3)-78 n-Pr OMe4-Me, 6-Me (3)-79 n-Pr OEt 3-F, 6-F (3)-80 n-Pr NO2 —

TABLE 9 No R3 Z1 (Z2)m (3)-81 n-Pr F 3-F (3)-82 n-Pr F 5-F (3)-83 n-Pr F6-F (3)-84 n-Pr F 3-Me, 6-F (3)-85 n-Pr F 3-OMe, 6-F (3)-86 n-Pr F3-OEt, 6-F (3)-87 n-Pr F 3-F, 5-Cl (3)-88 n-Pr F 3-F, 6-F (3)-89 n-Pr Cl— (3)-90 n-Pr Cl 6-Me (3)-91 n-Pr Cl 6-CF3 (3)-92 n-Pr Cl 5-Ph (3)-93n-Pr Cl 3-Cl (3)-94 n-Pr Cl 4-Cl (3)-95 n-Pr Cl 6-Cl (3)-96 n-Pr Cl 4-Br(3)-97 n-Pr Cl 6-Br (3)-98 n-Pr Cl 4-F (3)-99 n-Pr Cl 6-F (3)-100 n-PrCl 4-Me, 6-F (3)-101 n-Pr Cl 4-Me, 6-Cl (3)-102 n-Pr Cl 4-Me, 6-Br(3)-103 n-Pr Cl 4-Me, 6-F (3)-104 n-Pr Cl 4-Me, 6-OCF3 (3)-105 n-Pr Cl4-Me, 6-c-Pr (3)-106 n-Pr Cl 4-OCF3, 6-Cl (3)-107 n-Pr Cl 4-Cl, 6-Me(3)-108 n-Pr Cl 4-Cl, 6-Et (3)-109 n-Pr Cl 4-Cl, 6-c-Pr (3)-110 n-Pr Cl4-Cl, 6-OCF3 (3)-111 n-Pr Cl 4-Cl, 6-Br (3)-112 n-Pr Cl 4-Br, 6-Br(3)-113 n-Pr Cl 4-Br, 6-OCF3 (3)-114 n-Pr Cl 4-F, 6-F (3)-115 n-Pr Cl4-OMe, 6-Et (3)-116 n-Pr Br 4-Me, 6-Me (3)-117 n-Pr Br 4-Me, 6-Et(3)-118 n-Pr Br 4-Me, 6-Br (3)-119 n-Pr Br 4-Cl, 6-OCF3 (3)-120 n-Pr Br4-Br, 6-OCF3

TABLE 10 No R3 Z1 (Z2)m (4)-1 i-Pr Me 4-Me (4)-2 i-Pr Me 6-Me (4)-3 i-PrMe 4-Me, 6-Me (4)-4 i-Pr Me 4-Me, 6-Cl (4)-5 i-Pr Me 4-Cl (4)-6 i-Pr Me4-Cl, 6-Me (4)-7 i-Pr Me 4-Cl, 6-Br (4)-8 i-Pr Me 3-Br, 6-Me (4)-9 i-PrMe 4-Br, 6-Br (4)-10 i-Pr Me 4-F, 6-F (4)-11 i-Pr Me 3-(4-Cl—Ph) (4)-12i-Pr Me 5-Ph (4)-13 i-Pr Me 5-(2-Cl—Ph) (4)-14 i-Pr Me 5-(2-Br—Ph)(4)-15 i-Pr Me 5-(2-F—Ph) (4)-16 i-Pr Me 5-(2-OMe—Ph) (4)-17 i-Pr Me5-(2-Me—Ph) (4)-18 i-Pr Me 5-(2-CF3—Ph) (4)-19 i-Pr Me 5-(3-Cl—Ph)(4)-20 i-Pr Me 5-(3-Br—Ph) (4)-21 i-Pr Me 5-(3-F—Ph) (4)-22 i-Pr Me5-(3-OMe—Ph) (4)-23 i-Pr Me 5-(3-Me—Ph) (4)-24 i-Pr Me 5-(3-CF3—Ph)(4)-25 i-Pr Me 5-(4-Cl—Ph) (4)-26 i-Pr Me 5-(4-Br—Ph) (4)-27 i-Pr Me5-(4-F—Ph) (4)-28 i-Pr Me 5-(4-OMe—Ph) (4)-29 i-Pr Me 5-(4-Me—Ph) (4)-30i-Pr Me 5-(4-CF3—Ph) (4)-31 i-Pr CF3 5-CF3 (4)-32 i-Pr Et — (4)-33 i-PrEt 4-Me (4)-34 i-Pr Et 6-Me (4)-35 i-Pr Et 4-Me, 6-Me (4)-36 i-Pr Et4-Me, 6-OMe (4)-37 i-Pr Et 4-Et (4)-38 i-Pr Et 6-Et (4)-39 i-Pr Et 4-Me,6-Et (4)-40 i-Pr Et 4-Et, 6-Et

TABLE 11 No R3 Z1 (Z2)m (4)-41 i-Pr Et 4-C≡CH, 6-Et (4)-42 i-Pr Et4-c-Pr, 6-Et (4)-43 i-Pr Et 4-Ph, 6-Et (4)-44 i-Pr Et 4-Ph, 6-C≡CH(4)-45 i-Pr Et 4-Ph, 6-OMe (4)-46 i-Pr Et 4-(4-Me—Ph), 6-Et (4)-47 i-PrEt 4-(4-Cl—Ph), 6-Et (4)-48 i-Pr Et 4-CN, 6-Et (4)-49 i-Pr Et 4-OMe,6-Et (4)-50 i-Pr Et 4-NO2, 6-Et (4)-51 i-Pr Et 4-Cl, 6-Et (4)-52 i-Pr Et4-Br, 6-Et (4)-53 i-Pr Et 4-F, 6-Et (4)-54 i-Pr Et 5-Ph (4)-55 i-Pr Et5-(2-Cl—Ph) (4)-56 i-Pr Et 5-(2-Br—Ph) (4)-57 i-Pr Et 5-(2-F—Ph) (4)-58i-Pr Et 5-(2-OMe—Ph) (4)-59 i-Pr Et 5-(2-Me—Ph) (4)-60 i-Pr Et5-(2-CF3—Ph) (4)-61 i-Pr Et 5-(3-Cl—Ph) (4)-62 i-Pr Et 5-(3-Br—Ph)(4)-63 i-Pr Et 5-(3-F—Ph) (4)-64 i-Pr Et 5-(3-OMe—Ph) (4)-65 i-Pr Et5-(3-Me—Ph) (4)-66 i-Pr Et 5-(3-CF3—Ph) (4)-67 i-Pr Et 5-(4-Cl—Ph)(4)-68 i-Pr Et 5-(4-Br—Ph) (4)-69 i-Pr Et 5-(4-F—Ph) (4)-70 i-Pr Et5-(4-OMe—Ph) (4)-71 i-Pr Et 5-(4-Me—Ph) (4)-72 i-Pr Et 5-(4-CF3—Ph)(4)-73 i-Pr n-Pr — (4)-74 i-Pr c-Pr 4-Me, 6-Et (4)-75 i-Pr C≡CH 4-Me,6-Me (4)-76 i-Pr CN 4-Me, 6-Me (4)-77 i-Pr CN 4-Me, 6-Et (4)-78 i-Pr OMe4-Me, 6-Me (4)-79 i-Pr OEt 3-F, 6-F (4)-80 i-Pr NO2 —

TABLE 12 No R3 Z1 (Z2)m (4)-81 i-Pr F 3-F (4)-82 i-Pr F 5-F (4)-83 i-PrF 6-F (4)-84 i-Pr F 3-Me, 6-F (4)-85 i-Pr F 3-OMe, 6-F (4)-86 i-Pr F3-OEt, 6-F (4)-87 i-Pr F 3-F, 5-Cl (4)-88 i-Pr F 3-F, 6-F (4)-89 i-Pr Cl— (4)-90 i-Pr Cl 6-Me (4)-91 i-Pr Cl 6-CF3 (4)-92 i-Pr Cl 5-Ph (4)-93i-Pr Cl 3-Cl (4)-94 i-Pr Cl 4-Cl (4)-95 i-Pr Cl 6-Cl (4)-96 i-Pr Cl 4-Br(4)-97 i-Pr Cl 6-Br (4)-98 i-Pr Cl 4-F (4)-99 i-Pr Cl 6-F (4)-100 i-PrCl 4-Me, 6-F (4)-101 i-Pr Cl 4-Me, 6-Cl (4)-102 i-Pr Cl 4-Me, 6-Br(4)-103 i-Pr Cl 4-Me, 6-F (4)-104 i-Pr Cl 4-Me, 6-OCF3 (4)-105 i-Pr Cl4-Me, 6-c-Pr (4)-106 i-Pr Cl 4-OCF3, 6-Cl (4)-107 i-Pr Cl 4-Cl, 6-Me(4)-108 i-Pr Cl 4-Cl, 6-Et (4)-109 i-Pr Cl 4-Cl, 6-c-Pr (4)-110 i-Pr Cl4-Cl, 6-OCF3 (4)-111 i-Pr Cl 4-Cl, 6-Br (4)-112 i-Pr Cl 4-Br, 6-Br(4)-113 i-Pr Cl 4-Br, 6-OCF3 (4)-114 i-Pr Cl 4-F, 6-F (4)-115 i-Pr Cl4-OMe, 6-Et (4)-116 i-Pr Br 4-Me, 6-Me (4)-117 i-Pr Br 4-Me, 6-Et(4)-118 i-Pr Br 4-Me, 6-Br (4)-119 i-Pr Br 4-Cl, 6-OCF3 (4)-120 i-Pr Br4-Br, 6-OCF3

TABLE 13 No R3 Z1 (Z2)m (5)-1 CH2CH2OMe Me 4-Me (5)-2 CH2CH2OMe Me 6-Me(5)-3 CH2CH2OMe Me 4-Me, 6-Me (5)-4 CH2CH2OMe Me 4-Me, 6-Cl (5)-5CH2CH2OMe Me 4-Cl (5)-6 CH2CH2OMe Me 4-Cl, 6-Me (5)-7 CH2CH2OMe Me 4-Cl,6-Br (5)-8 CH2CH2OMe Me 3-Br, 6-Me (5)-9 CH2CH2OMe Me 4-Br, 6-Br (5)-10CH2CH2OMe Me 4-F, 6-F (5)-11 CH2CH2OMe Me 3-(4-Cl—Ph) (5)-12 CH2CH2OMeMe 5-Ph (5)-13 CH2CH2OMe Me 5-(2-Cl—Ph) (5)-14 CH2CH2OMe Me 5-(2-Br—Ph)(5)-15 CH2CH2OMe Me 5-(2-F—Ph) (5)-16 CH2CH2OMe Me 5-(2-OMe—Ph) (5)-17CH2CH2OMe Me 5-(2-Me—Ph) (5)-18 CH2CH2OMe Me 5-(2-CF3—Ph) (5)-19CH2CH2OMe Me 5-(3-Cl—Ph) (5)-20 CH2CH2OMe Me 5-(3-Br—Ph) (5)-21CH2CH2OMe Me 5-(3-F—Ph) (5)-22 CH2CH2OMe Me 5-(3-OMe—Ph) (5)-23CH2CH2OMe Me 5-(3-Me—Ph) (5)-24 CH2CH2OMe Me 5-(3-CF3—Ph) (5)-25CH2CH2OMe Me 5-(4-Cl—Ph) (5)-26 CH2CH2OMe Me 5-(4-Br—Ph) (5)-27CH2CH2OMe Me 5-(4-F—Ph) (5)-28 CH2CH2OMe Me 5-(4-OMe—Ph) (5)-29CH2CH2OMe Me 5-(4-Me—Ph) (5)-30 CH2CH2OMe Me 5-(4-CF3—Ph) (5)-31CH2CH2OMe CF3 5-CF3 (5)-32 CH2CH2OMe Et — (5)-33 CH2CH2OMe Et 4-Me(5)-34 CH2CH2OMe Et 6-Me (5)-35 CH2CH2OMe Et 4-Me, 6-Me (5)-36 CH2CH2OMeEt 4-Me, 6-OMe (5)-37 CH2CH2OMe Et 4-Et (5)-38 CH2CH2OMe Et 6-Et (5)-39CH2CH2OMe Et 4-Me, 6-Et (5)-40 CH2CH2OMe Et 4-Et, 6-Et

TABLE 14 No R3 Z1 (Z2)m (5)-41 CH2CH2OMe Et 4-C≡CH, 6-Et (5)-42CH2CH2OMe Et 4-c-Pr, 6-Et (5)-43 CH2CH2OMe Et 4-Ph, 6-Et (5)-44CH2CH2OMe Et 4-Ph, 6-C≡CH (5)-45 CH2CH2OMe Et 4-Ph, 6-OMe (5)-46CH2CH2OMe Et 4-(4-Me—Ph), 6-Et (5)-47 CH2CH2OMe Et 4-(4-Cl—Ph), 6-Et(5)-48 CH2CH2OMe Et 4-CN, 6-Et (5)-49 CH2CH2OMe Et 4-OMe, 6-Et (5)-50CH2CH2OMe Et 4-NO2, 6-Et (5)-51 CH2CH2OMe Et 4-Cl, 6-Et (5)-52 CH2CH2OMeEt 4-Br, 6-Et (5)-53 CH2CH2OMe Et 4-F, 6-Et (5)-54 CH2CH2OMe Et 5-Ph(5)-55 CH2CH2OMe Et 5-(2-Cl—Ph) (5)-56 CH2CH2OMe Et 5-(2-Br—Ph) (5)-57CH2CH2OMe Et 5-(2-F—Ph) (5)-58 CH2CH2OMe Et 5-(2-OMe—Ph) (5)-59CH2CH2OMe Et 5-(2-Me—Ph) (5)-60 CH2CH2OMe Et 5-(2-CF3—Ph) (5)-61CH2CH2OMe Et 5-(3-Cl—Ph) (5)-62 CH2CH2OMe Et 5-(3-Br—Ph) (5)-63CH2CH2OMe Et 5-(3-F—Ph) (5)-64 CH2CH2OMe Et 5-(3-OMe—Ph) (5)-65CH2CH2OMe Et 5-(3-Me—Ph) (5)-66 CH2CH2OMe Et 5-(3-CF3—Ph) (5)-67CH2CH2OMe Et 5-(4-Cl—Ph) (5)-68 CH2CH2OMe Et 5-(4-Br—Ph) (5)-69CH2CH2OMe Et 5-(4-F—Ph) (5)-70 CH2CH2OMe Et 5-(4-OMe—Ph) (5)-71CH2CH2OMe Et 5-(4-Me—Ph) (5)-72 CH2CH2OMe Et 5-(4-CF3—Ph) (5)-73CH2CH2OMe n-Pr — (5)-74 CH2CH2OMe c-Pr 4-Me, 6-Et (5)-75 CH2CH2OMe C≡CH4-Me, 6-Me (5)-76 CH2CH2OMe CN 4-Me, 6-Me (5)-77 CH2CH2OMe CN 4-Me, 6-Et(5)-78 CH2CH2OMe OMe 4-Me, 6-Me (5)-79 CH2CH2OMe OEt 3-F, 6-F (5)-80CH2CH2OMe NO2 —

TABLE 15 No R3 Z1 (Z2)m (5)-81 CH2CH2OMe F 3-F (5)-82 CH2CH2OMe F 5-F(5)-83 CH2CH2OMe F 6-F (5)-84 CH2CH2OMe F 3-Me, 6-F (5)-85 CH2CH2OMe F3-OMe, 6-F (5)-86 CH2CH2OMe F 3-OEt, 6-F (5)-87 CH2CH2OMe F 3-F, 5-Cl(5)-88 CH2CH2OMe F 3-F, 6-F (5)-89 CH2CH2OMe Cl — (5)-90 CH2CH2OMe Cl6-Me (5)-91 CH2CH2OMe Cl 6-CF3 (5)-92 CH2CH2OMe Cl 5-Ph (5)-93 CH2CH2OMeCl 3-Cl (5)-94 CH2CH2OMe Cl 4-Cl (5)-95 CH2CH2OMe Cl 6-Cl (5)-96CH2CH2OMe Cl 4-Br (5)-97 CH2CH2OMe Cl 6-Br (5)-98 CH2CH2OMe Cl 4-F(5)-99 CH2CH2OMe Cl 6-F (5)-100 CH2CH2OMe Cl 4-Me, 6-F (5)-101 CH2CH2OMeCl 4-Me, 6-Cl (5)-102 CH2CH2OMe Cl 4-Me, 6-Br (5)-103 CH2CH2OMe Cl 4-Me,6-F (5)-104 CH2CH2OMe Cl 4-Me, 6-OCF3 (5)-105 CH2CH2OMe Cl 4-Me, 6-c-Pr(5)-106 CH2CH2OMe Cl 4-OCF3, 6-Cl (5)-107 CH2CH2OMe Cl 4-Cl, 6-Me(5)-108 CH2CH2OMe Cl 4-Cl, 6-Et (5)-109 CH2CH2OMe Cl 4-Cl, 6-c-Pr(5)-110 CH2CH2OMe Cl 4-Cl, 6-OCF3 (5)-111 CH2CH2OMe Cl 4-Cl, 6-Br(5)-112 CH2CH2OMe Cl 4-Br, 6-Br (5)-113 CH2CH2OMe Cl 4-Br, 6-OCF3(5)-114 CH2CH2OMe Cl 4-F, 6-F (5)-115 CH2CH2OMe Cl 4-OMe, 6-Et (5)-116CH2CH2OMe Br 4-Me, 6-Me (5)-117 CH2CH2OMe Br 4-Me, 6-Et (5)-118CH2CH2OMe Br 4-Me, 6-Br (5)-119 CH2CH2OMe Br 4-Cl, 6-OCF3 (5)-120CH2CH2OMe Br 4-Br, 6-OCF3

TABLE 16 No R3 Z1 (Z2)m (6)-1 CH2CH2OEt Me 4-Me (6)-2 CH2CH2OEt Me 6-Me(6)-3 CH2CH2OEt Me 4-Me, 6-Me (6)-4 CH2CH2OEt Me 4-Me, 6-Cl (6)-5CH2CH2OEt Me 4-Cl (6)-6 CH2CH2OEt Me 4-Cl, 6-Me (6)-7 CH2CH2OEt Me 4-Cl,6-Br (6)-8 CH2CH2OEt Me 3-Br, 6-Me (6)-9 CH2CH2OEt Me 4-Br, 6-Br (6)-10CH2CH2OEt Me 4-F, 6-F (6)-11 CH2CH2OEt Me 3-(4-Cl—Ph) (6)-12 CH2CH2OEtMe 5-Ph (6)-13 CH2CH2OEt Me 5-(2-Cl—Ph) (6)-14 CH2CH2OEt Me 5-(2-Br—Ph)(6)-15 CH2CH2OEt Me 5-(2-F—Ph) (6)-16 CH2CH2OEt Me 5-(2-OMe—Ph) (6)-17CH2CH2OEt Me 5-(2-Me—Ph) (6)-18 CH2CH2OEt Me 5-(2-CF3—Ph) (6)-19CH2CH2OEt Me 5-(3-Cl—Ph) (6)-20 CH2CH2OEt Me 5-(3-Br—Ph) (6)-21CH2CH2OEt Me 5-(3-F—Ph) (6)-22 CH2CH2OEt Me 5-(3-OMe—Ph) (6)-23CH2CH2OEt Me 5-(3-Me—Ph) (6)-24 CH2CH2OEt Me 5-(3-CF3—Ph) (6)-25CH2CH2OEt Me 5-(4-Cl—Ph) (6)-26 CH2CH2OEt Me 5-(4-Br—Ph) (6)-27CH2CH2OEt Me 5-(4-F—Ph) (6)-28 CH2CH2OEt Me 5-(4-OMe—Ph) (6)-29CH2CH2OEt Me 5-(4-Me—Ph) (6)-30 CH2CH2OEt Me 5-(4-CF3—Ph) (6)-31CH2CH2OEt CF3 5-CF3 (6)-32 CH2CH2OEt Et — (6)-33 CH2CH2OEt Et 4-Me(6)-34 CH2CH2OEt Et 6-Me (6)-35 CH2CH2OEt Et 4-Me, 6-Me (6)-36 CH2CH2OEtEt 4-Me, 6-OMe (6)-37 CH2CH2OEt Et 4-Et (6)-38 CH2CH2OEt Et 6-Et (6)-39CH2CH2OEt Et 4-Me, 6-Et (6)-40 CH2CH2OEt Et 4-Et, 6-Et

TABLE 17 No R3 Z1 (Z2)m (6)-41 CH2CH2OEt Et 4-C≡CH, 6-Et (6)-42CH2CH2OEt Et 4-c-Pr, 6-Et (6)-43 CH2CH2OEt Et 4-Ph, 6-Et (6)-44CH2CH2OEt Et 4-Ph, 6-C≡CH (6)-45 CH2CH2OEt Et 4-Ph, 6-OMe (6)-46CH2CH2OEt Et 4-(4-Me—Ph), 6-Et (6)-47 CH2CH2OEt Et 4-(4-Cl—Ph), 6-Et(6)-48 CH2CH2OEt Et 4-CN, 6-Et (6)-49 CH2CH2OEt Et 4-OMe, 6-Et (6)-50CH2CH2OEt Et 4-NO2, 6-Et (6)-51 CH2CH2OEt Et 4-Cl, 6-Et (6)-52 CH2CH2OEtEt 4-Br, 6-Et (6)-53 CH2CH2OEt Et 4-F, 6-Et (6)-54 CH2CH2OEt Et 5-Ph(6)-55 CH2CH2OEt Et 5-(2-Cl—Ph) (6)-56 CH2CH2OEt Et 5-(2-Br—Ph) (6)-57CH2CH2OEt Et 5-(2-F—Ph) (6)-58 CH2CH2OEt Et 5-(2-OMe—Ph) (6)-59CH2CH2OEt Et 5-(2-Me—Ph) (6)-60 CH2CH2OEt Et 5-(2-CF3—Ph) (6)-61CH2CH2OEt Et 5-(3-Cl—Ph) (6)-62 CH2CH2OEt Et 5-(3-Br—Ph) (6)-63CH2CH2OEt Et 5-(3-F—Ph) (6)-64 CH2CH2OEt Et 5-(3-OMe—Ph) (6)-65CH2CH2OEt Et 5-(3-Me—Ph) (6)-66 CH2CH2OEt Et 5-(3-CF3—Ph) (6)-67CH2CH2OEt Et 5-(4-Cl—Ph) (6)-68 CH2CH2OEt Et 5-(4-Br—Ph) (6)-69CH2CH2OEt Et 5-(4-F—Ph) (6)-70 CH2CH2OEt Et 5-(4-OMe—Ph) (6)-71CH2CH2OEt Et 5-(4-Me—Ph) (6)-72 CH2CH2OEt Et 5-(4-CF3—Ph) (6)-73CH2CH2OEt n-Pr — (6)-74 CH2CH2OEt c-Pr 4-Me, 6-Et (6)-75 CH2CH2OEt C≡CH4-Me, 6-Me (6)-76 CH2CH2OEt CN 4-Me, 6-Me (6)-77 CH2CH2OEt CN 4-Me, 6-Et(6)-78 CH2CH2OEt OMe 4-Me, 6-Me (6)-79 CH2CH2OEt OEt 3-F, 6-F (6)-80CH2CH2OEt NO2 —

TABLE 18 No R3 Z1 (Z2)m (6)-81 CH2CH2OEt F 3-F (6)-82 CH2CH2OEt F 5-F(6)-83 CH2CH2OEt F 6-F (6)-84 CH2CH2OEt F 3-Me, 6-F (6)-85 CH2CH2OEt F3-OMe, 6-F (6)-86 CH2CH2OEt F 3-OEt, 6-F (6)-87 CH2CH2OEt F 3-F, 5-Cl(6)-88 CH2CH2OEt F 3-F, 6-F (6)-89 CH2CH2OEt Cl — (6)-90 CH2CH2OEt Cl6-Me (6)-91 CH2CH2OEt Cl 6-CF3 (6)-92 CH2CH2OEt Cl 5-Ph (6)-93 CH2CH2OEtCl 3-Cl (6)-94 CH2CH2OEt Cl 4-Cl (6)-95 CH2CH2OEt Cl 6-Cl (6)-96CH2CH2OEt Cl 4-Br (6)-97 CH2CH2OEt Cl 6-Br (6)-98 CH2CH2OEt Cl 4-F(6)-99 CH2CH2OEt Cl 6-F (6)-100 CH2CH2OEt Cl 4-Me, 6-F (6)-101 CH2CH2OEtCl 4-Me, 6-Cl (6)-102 CH2CH2OEt Cl 4-Me, 6-Br (6)-103 CH2CH2OEt Cl 4-Me,6-F (6)-104 CH2CH2OEt Cl 4-Me, 6-OCF3 (6)-105 CH2CH2OEt Cl 4-Me, 6-c-Pr(6)-106 CH2CH2OEt Cl 4-OCF3, 6-Cl (6)-107 CH2CH2OEt Cl 4-Cl, 6-Me(6)-108 CH2CH2OEt Cl 4-Cl, 6-Et (6)-109 CH2CH2OEt Cl 4-Cl, 6-c-Pr(6)-110 CH2CH2OEt Cl 4-Cl, 6-OCF3 (6)-111 CH2CH2OEt Cl 4-Cl, 6-Br(6)-112 CH2CH2OEt Cl 4-Br, 6-Br (6)-113 CH2CH2OEt Cl 4-Br, 6-OCF3(6)-114 CH2CH2OEt Cl 4-F, 6-F (6)-115 CH2CH2OEt Cl 4-OMe, 6-Et (6)-116CH2CH2OEt Br 4-Me, 6-Me (6)-117 CH2CH2OEt Br 4-Me, 6-Et (6)-118CH2CH2OEt Br 4-Me, 6-Br (6)-119 CH2CH2OEt Br 4-Cl, 6-OCF3 (6)-120CH2CH2OEt Br 4-Br, 6-OCF3

TABLE 19 No R3 Z1 (Z2)m (7)-1 CH2Ph Me 4-Me (7)-2 CH2Ph Me 6-Me (7)-3CH2Ph Me 4-Me, 6-Me (7)-4 CH2Ph Me 4-Me, 6-Cl (7)-5 CH2Ph Me 4-Cl (7)-6CH2Ph Me 4-Cl, 6-Me (7)-7 CH2Ph Me 4-Cl, 6-Br (7)-8 CH2Ph Me 3-Br, 6-Me(7)-9 CH2Ph Me 4-Br, 6-Br (7)-10 CH2Ph Me 4-F, 6-F (7)-11 CH2Ph Me3-(4-Cl—Ph) (7)-12 CH2Ph Me 5-Ph (7)-13 CH2Ph Me 5-(2-Cl—Ph) (7)-14CH2Ph Me 5-(2-Br—Ph) (7)-15 CH2Ph Me 5-(2-F—Ph) (7)-16 CH2Ph Me5-(2-OMe—Ph) (7)-17 CH2Ph Me 5-(2-Me—Ph) (7)-18 CH2Ph Me 5-(2-CF3—Ph)(7)-19 CH2Ph Me 5-(3-Cl—Ph) (7)-20 CH2Ph Me 5-(3-Br—Ph) (7)-21 CH2Ph Me5-(3-F—Ph) (7)-22 CH2Ph Me 5-(3-OMe—Ph) (7)-23 CH2Ph Me 5-(3-Me—Ph)(7)-24 CH2Ph Me 5-(3-CF3—Ph) (7)-25 CH2Ph Me 5-(4-Cl—Ph) (7)-26 CH2Ph Me5-(4-Br—Ph) (7)-27 CH2Ph Me 5-(4-F—Ph) (7)-28 CH2Ph Me 5-(4-OMe—Ph)(7)-29 CH2Ph Me 5-(4-Me—Ph) (7)-30 CH2Ph Me 5-(4-CF3—Ph) (7)-31 CH2PhCF3 5-CF3 (7)-32 CH2Ph Et — (7)-33 CH2Ph Et 4-Me (7)-34 CH2Ph Et 6-Me(7)-35 CH2Ph Et 4-Me, 6-Me (7)-36 CH2Ph Et 4-Me, 6-OMe (7)-37 CH2Ph Et4-Et (7)-38 CH2Ph Et 6-Et (7)-39 CH2Ph Et 4-Me, 6-Et (7)-40 CH2Ph Et4-Et, 6-Et

TABLE 20 No R3 Z1 (Z2)m (7)-41 CH2Ph Et 4-C≡CH, 6-Et (7)-42 CH2Ph Et4-c-Pr, 6-Et (7)-43 CH2Ph Et 4-Ph, 6-Et (7)-44 CH2Ph Et 4-Ph, 6-C≡CH(7)-45 CH2Ph Et 4-Ph, 6-OMe (7)-46 CH2Ph Et 4-(4-Me—Ph), 6-Et (7)-47CH2Ph Et 4-(4-Cl—Ph), 6-Et (7)-48 CH2Ph Et 4-CN, 6-Et (7)-49 CH2Ph Et4-OMe, 6-Et (7)-50 CH2Ph Et 4-NO2, 6-Et (7)-51 CH2Ph Et 4-Cl, 6-Et(7)-52 CH2Ph Et 4-Br, 6-Et (7)-53 CH2Ph Et 4-F, 6-Et (7)-54 CH2Ph Et5-Ph (7)-55 CH2Ph Et 5-(2-Cl—Ph) (7)-56 CH2Ph Et 5-(2-Br—Ph) (7)-57CH2Ph Et 5-(2-F—Ph) (7)-58 CH2Ph Et 5-(2-OMe—Ph) (7)-59 CH2Ph Et5-(2-Me—Ph) (7)-60 CH2Ph Et 5-(2-CF3—Ph) (7)-61 CH2Ph Et 5-(3-Cl—Ph)(7)-62 CH2Ph Et 5-(3-Br—Ph) (7)-63 CH2Ph Et 5-(3-F—Ph) (7)-64 CH2Ph Et5-(3-OMe—Ph) (7)-65 CH2Ph Et 5-(3-Me—Ph) (7)-66 CH2Ph Et 5-(3-CF3—Ph)(7)-67 CH2Ph Et 5-(4-Cl—Ph) (7)-68 CH2Ph Et 5-(4-Br—Ph) (7)-69 CH2Ph Et5-(4-F—Ph) (7)-70 CH2Ph Et 5-(4-OMe—Ph) (7)-71 CH2Ph Et 5-(4-Me—Ph)(7)-72 CH2Ph Et 5-(4-CF3—Ph) (7)-73 CH2Ph n-Pr — (7)-74 CH2Ph c-Pr 4-Me,6-Et (7)-75 CH2Ph C≡CH 4-Me, 6-Me (7)-76 CH2Ph CN 4-Me, 6-Me (7)-77CH2Ph CN 4-Me, 6-Et (7)-78 CH2Ph OMe 4-Me, 6-Me (7)-79 CH2Ph OEt 3-F,6-F (7)-80 CH2Ph NO2 —

TABLE 21 No R3 Z1 (Z2)m (7)-81 CH2Ph F 3-F (7)-82 CH2Ph F 5-F (7)-83CH2Ph F 6-F (7)-84 CH2Ph F 3-Me, 6-F (7)-85 CH2Ph F 3-OMe, 6-F (7)-86CH2Ph F 3-OEt, 6-F (7)-87 CH2Ph F 3-F, 5-Cl (7)-88 CH2Ph F 3-F, 6-F(7)-89 CH2Ph Cl — (7)-90 CH2Ph Cl 6-Me (7)-91 CH2Ph Cl 6-CF3 (7)-92CH2Ph Cl 5-Ph (7)-93 CH2Ph Cl 3-Cl (7)-94 CH2Ph Cl 4-Cl (7)-95 CH2Ph Cl6-Cl (7)-96 CH2Ph Cl 4-Br (7)-97 CH2Ph Cl 6-Br (7)-98 CH2Ph Cl 4-F(7)-99 CH2Ph Cl 6-F (7)-100 CH2Ph Cl 4-Me, 6-F (7)-101 CH2Ph Cl 4-Me,6-Cl (7)-102 CH2Ph Cl 4-Me, 6-Br (7)-103 CH2Ph Cl 4-Me, 6-F (7)-104CH2Ph Cl 4-Me, 6-OCF3 (7)-105 CH2Ph Cl 4-Me, 6-c-Pr (7)-106 CH2Ph Cl4-OCF3, 6-Cl (7)-107 CH2Ph Cl 4-Cl, 6-Me (7)-108 CH2Ph Cl 4-Cl, 6-Et(7)-109 CH2Ph Cl 4-Cl, 6-c-Pr (7)-110 CH2Ph Cl 4-Cl, 6-OCF3 (7)-111CH2Ph Cl 4-Cl, 6-Br (7)-112 CH2Ph Cl 4-Br, 6-Br (7)-113 CH2Ph Cl 4-Br,6-OCF3 (7)-114 CH2Ph Cl 4-F, 6-F (7)-115 CH2Ph Cl 4-OMe, 6-Et (7)-116CH2Ph Br 4-Me, 6-Me (7)-117 CH2Ph Br 4-Me, 6-Et (7)-118 CH2Ph Br 4-Me,6-Br (7)-119 CH2Ph Br 4-Cl, 6-OCF3 (7)-120 CH2Ph Br 4-Br, 6-OCF3

TABLE 22 No R3 Z1 (Z2)m (8)-1 H Me 4-Me (8)-2 H Me 6-Me (8)-3 H Me 4-Me,6-Me (8)-4 H Me 4-Me, 6-Cl (8)-5 H Me 4-Cl (8)-6 H Me 4-Cl, 6-Me (8)-7 HMe 4-Cl, 6-Br (8)-8 H Me 3-Br, 6-Me (8)-9 H Me 4-Br, 6-Br (8)-10 H Me4-F, 6-F (8)-11 H Me 3-(4-Cl—Ph) (8)-12 H Me 5-Ph (8)-13 H Me5-(2-Cl—Ph) (8)-14 H Me 5-(2-Br—Ph) (8)-15 H Me 5-(2-F—Ph) (8)-16 H Me5-(2-OMe—Ph) (8)-17 H Me 5-(2-Me—Ph) (8)-18 H Me 5-(2-CF3—Ph) (8)-19 HMe 5-(3-Cl—Ph) (8)-20 H Me 5-(3-Br—Ph) (8)-21 H Me 5-(3-F—Ph) (8)-22 HMe 5-(3-OMe—Ph) (8)-23 H Me 5-(3-Me—Ph) (8)-24 H Me 5-(3-CF3—Ph) (8)-25H Me 5-(4-Cl—Ph) (8)-26 H Me 5-(4-Br—Ph) (8)-27 H Me 5-(4-F—Ph) (8)-28 HMe 5-(4-OMe—Ph) (8)-29 H Me 5-(4-Me—Ph) (8)-30 H Me 5-(4-CF3—Ph) (8)-31H CF3 5-CF3 (8)-32 H Et — (8)-33 H Et 4-Me (8)-34 H Et 6-Me (8)-35 H Et4-Me, 6-Me (8)-36 H Et 4-Me, 6-OMe (8)-37 H Et 4-Et (8)-38 H Et 6-Et(8)-39 H Et 4-Me, 6-Et (8)-40 H Et 4-Et, 6-Et

TABLE 23 No R3 Z1 (Z2)m (8)-41 H Et 4-C≡CH, 6-Et (8)-42 H Et 4-c-Pr,6-Et (8)-43 H Et 4-Ph, 6-Et (8)-44 H Et 4-Ph, 6-C≡CH (8)-45 H Et 4-Ph,6-OMe (8)-46 H Et 4-(4-Me—Ph), 6-Et (8)-47 H Et 4-(4-Cl—Ph), 6-Et (8)-48H Et 4-CN, 6-Et (8)-49 H Et 4-OMe, 6-Et (8)-50 H Et 4-NO2, 6-Et (8)-51 HEt 4-Cl, 6-Et (8)-52 H Et 4-Br, 6-Et (8)-53 H Et 4-F, 6-Et (8)-54 H Et5-Ph (8)-55 H Et 5-(2-Cl—Ph) (8)-56 H Et 5-(2-Br—Ph) (8)-57 H Et5-(2-F—Ph) (8)-58 H Et 5-(2-OMe—Ph) (8)-59 H Et 5-(2-Me—Ph) (8)-60 H Et5-(2-CF3—Ph) (8)-61 H Et 5-(3-Cl—Ph) (8)-62 H Et 5-(3-Br—Ph) (8)-63 H Et5-(3-F—Ph) (8)-64 H Et 5-(3-OMe—Ph) (8)-65 H Et 5-(3-Me—Ph) (8)-66 H Et5-(3-CF3—Ph) (8)-67 H Et 5-(4-Cl—Ph) (8)-68 H Et 5-(4-Br—Ph) (8)-69 H Et5-(4-F—Ph) (8)-70 H Et 5-(4-OMe—Ph) (8)-71 H Et 5-(4-Me—Ph) (8)-72 H Et5-(4-CF3—Ph) (8)-73 H n-Pr — (8)-74 H c-Pr 4-Me, 6-Et (8)-75 H C≡CH4-Me, 6-Me (8)-76 H CN 4-Me, 6-Me (8)-77 H CN 4-Me, 6-Et (8)-78 H OMe4-Me, 6-Me (8)-79 H OEt 3-F, 6-F (8)-80 H NO2 —

TABLE 24 No R3 Z1 (Z2)m (8)-81 H F 3-F (8)-82 H F 5-F (8)-83 H F 6-F(8)-84 H F 3-Me, 6-F (8)-85 H F 3-OMe, 6-F (8)-86 H F 3-OEt, 6-F (8)-87H F 3-F, 5-Cl (8)-88 H F 3-F, 6-F (8)-89 H Cl — (8)-90 H Cl 6-Me (8)-91H Cl 6-CF3 (8)-92 H Cl 5-Ph (8)-93 H Cl 3-Cl (8)-94 H Cl 4-Cl (8)-95 HCl 6-Cl (8)-96 H Cl 4-Br (8)-97 H Cl 6-Br (8)-98 H Cl 4-F (8)-99 H Cl6-F (8)-100 H Cl 4-Me, 6-F (8)-101 H Cl 4-Me, 6-Cl (8)-102 H Cl 4-Me,6-Br (8)-103 H Cl 4-Me, 6-F (8)-104 H Cl 4-Me, 6-OCF3 (8)-105 H Cl 4-Me,6-c-Pr (8)-106 H Cl 4-OCF3, 6-Cl (8)-107 H Cl 4-Cl, 6-Me (8)-108 H Cl4-Cl, 6-Et (8)-109 H Cl 4-Cl, 6-c-Pr (8)-110 H Cl 4-Cl, 6-OCF3 (8)-111 HCl 4-Cl, 6-Br (8)-112 H Cl 4-Br, 6-Br (8)-113 H Cl 4-Br, 6-OCF3 (8)-114H Cl 4-F, 6-F (8)-115 H Cl 4-OMe, 6-Et (8)-116 H Br 4-Me, 6-Me (8)-117 HBr 4-Me, 6-Et (8)-118 H Br 4-Me, 6-Br (8)-119 H Br 4-Cl, 6-OCF3 (8)-120H Br 4-Br, 6-OCF3

TABLE 25 No. R3 Z³ (Z⁴)_(r) (9)-1 Me Me 4-CF3 (9)-2 Me Me 4-Cl (9)-3 MeMe 4-Br (9)-4 Me Me 4-F (9)-5 Me Et 4-CF3 (9)-6 Me Et 4-Cl (9)-7 Me Et4-Br (9)-8 Me Et 4-F (9)-9 Et Me 4-CF3 (9)-10 Et Me 4-Cl (9)-11 Et Me4-Br (9)-12 Et Me 4-F (9)-13 Et Et 4-CF3 (9)-14 Et Et 4-Cl (9)-15 Et Et4-Br (9)-16 Et Et 4-F (9)-17 n-Pr Me 4-CF3 (9)-18 n-Pr Me 4-Cl (9)-19n-Pr Me 4-Br (9)-20 n-Pr Me 4-F (9)-21 n-Pr Et 4-CF3 (9)-22 n-Pr Et 4-Cl(9)-24 n-Pr Et 4-Br (9)-24 n-Pr Et 4-F (9)-25 i-Pr Me 4-CF3 (9)-26 i-PrMe 4-Cl (9)-27 i-Pr Me 4-Br (9)-28 i-Pr Me 4-F (9)-29 i-Pr Et 4-CF3(9)-30 i-Pr Et 4-Cl (9)-31 i-Pr Et 4-Br (9)-32 i-Pr Et 4-F (9)-33CH2CH2OMe Me 4-CF3 (9)-34 CH2CH2OMe Me 4-Cl (9)-35 CH2CH2OMe Me 4-Br(9)-36 CH2CH2OMe Me 4-F (9)-37 CH2CH2OMe Et 4-CF3 (9)-38 CH2CH2OMe Et4-Cl (9)-39 CH2CH2OMe Et 4-Br (9)-40 CH2CH2OMe Et 4-F

TABLE 26 No. R3 Z³ (Z⁴)_(r) (10)-1 CH2CH2OEt Me 4-CF3 (10)-2 CH2CH2OEtMe 4-Cl (10)-3 CH2CH2OEt Me 4-Br (10)-4 CH2CH2OEt Me 4-F (10)-5CH2CH2OEt Et 4-CF3 (10)-6 CH2CH2OEt Et 4-Cl (10)-7 CH2CH2OEt Et 4-Br(10)-8 CH2CH2OEt Et 4-F (10)-9 CH2Ph Me 4-CF3 (10)-10 CH2Ph Me 4-Cl(10)-11 CH2Ph Me 4-Br (10)-12 CH2Ph Me 4-F (10)-13 CH2Ph Et 4-CF3(10)-14 CH2Ph Et 4-Cl (10)-15 CH2Ph Et 4-Br (10)-16 CH2Ph Et 4-F

TABLE 27 No Z1 (Z2)m (11)-1 Me 4-Me (11)-2 Me 6-Me (11)-3 Me 4-Me, 6-Me(11)-4 Me 4-Me, 6-Cl (11)-5 Me 4-Cl (11)-6 Me 4-Cl, 6-Me (11)-7 Me 4-Cl,6-Br (11)-8 Me 3-Br, 6-Me (11)-9 Me 4-Br, 6-Br (11)-10 Me 4-F, 6-F(11)-11 Me 3-(4-Cl—Ph) (11)-12 Me 5-Ph (11)-13 Me 5-(2-Cl—Ph) (11)-14 Me5-(2-Br—Ph) (11)-15 Me 5-(2-F—Ph) (11)-16 Me 5-(2-OMe—Ph) (11)-17 Me5-(2-Me—Ph) (11)-18 Me 5-(2-CF3—Ph) (11)-19 Me 5-(3-Cl—Ph) (11)-20 Me5-(3-Br—Ph) (11)-21 Me 5-(3-F—Ph) (11)-22 Me 5-(3-OMe—Ph) (11)-23 Me5-(3-Me—Ph) (11)-24 Me 5-(3-CF3—Ph) (11)-25 Me 5-(4-Cl—Ph) (11)-26 Me5-(4-Br—Ph) (11)-27 Me 5-(4-F—Ph) (11)-28 Me 5-(4-OMe—Ph) (11)-29 Me5-(4-Me—Ph) (11)-30 Me 5-(4-CF3—Ph) (11)-31 CF3 5-CF3 (11)-32 Et —(11)-33 Et 4-Me (11)-34 Et 6-Me (11)-35 Et 4-Me, 6-Me (11)-36 Et 4-Me,6-OMe (11)-37 Et 4-Et (11)-38 Et 6-Et (11)-39 Et 4-Me, 6-Et (11)-40 Et4-Et, 6-Et

TABLE 28 No Z1 (Z2)m (11)-41 Et 4-C≡CH, 6-Et (11)-42 Et 4-c-Pr, 6-Et(11)-43 Et 4-Ph, 6-Et (11)-44 Et 4-Ph, 6-C≡CH (11)-45 Et 4-Ph, 6-OMe(11)-46 Et 4-(4-Me—Ph), 6-Et (11)-47 Et 4-(4-Cl—Ph), 6-Et (11)-48 Et4-CN, 6-Et (11)-49 Et 4-OMe, 6-Et (11)-50 Et 4-NO2, 6-Et (11)-51 Et4-Cl, 6-Et (11)-52 Et 4-Br, 6-Et (11)-53 Et 4-F, 6-Et (11)-54 Et 5-Ph(11)-55 Et 5-(2-Cl—Ph) (11)-56 Et 5-(2-Br—Ph) (11)-57 Et 5-(2-F—Ph)(11)-58 Et 5-(2-OMe—Ph) (11)-59 Et 5-(2-Me—Ph) (11)-60 Et 5-(2-CF3—Ph)(11)-61 Et 5-(3-Cl—Ph) (11)-62 Et 5-(3-Br—Ph) (11)-63 Et 5-(3-F—Ph)(11)-64 Et 5-(3-OMe—Ph) (11)-65 Et 5-(3-Me—Ph) (11)-66 Et 5-(3-CF3—Ph)(11)-67 Et 5-(4-Cl—Ph) (11)-68 Et 5-(4-Br—Ph) (11)-69 Et 5-(4-F—Ph)(11)-70 Et 5-(4-OMe—Ph) (11)-71 Et 5-(4-Me—Ph) (11)-72 Et 5-(4-CF3—Ph)(11)-73 n-Pr — (11)-74 c-Pr 4-Me, 6-Et (11)-75 C≡CH 4-Me, 6-Me (11)-76CN 4-Me, 6-Me (11)-77 CN 4-Me, 6-Et (11)-78 OMe 4-Me, 6-Me (11)-79 OEt3-F, 6-F (11)-80 NO2 —

TABLE 29 No Z1 (Z2)m (11)-81 F 3-F (11)-82 F 5-F (11)-83 F 6-F (11)-84 F3-Me, 6-F (11)-85 F 3-OMe, 6-F (11)-86 F 3-OEt, 6-F (11)-87 F 3-F, 5-Cl(11)-88 F 3-F, 6-F (11)-89 Cl — (11)-90 Cl 6-Me (11)-91 Cl 6-CF3 (11)-92Cl 5-Ph (11)-93 Cl 3-Cl (11)-94 Cl 4-Cl (11)-95 Cl 6-Cl (11)-96 Cl 4-Br(11)-97 Cl 6-Br (11)-98 Cl 4-F (11)-99 Cl 6-F (11)-100 Cl 4-Me, 6-F(11)-101 Cl 4-Me, 6-Cl (11)-102 Cl 4-Me, 6-Br (11)-103 Cl 4-Me, 6-F(11)-104 Cl 4-Me, 6-OCF3 (11)-105 Cl 4-Me, 6-c-Pr (11)-106 Cl 4-OCF3,6-Cl (11)-107 Cl 4-Cl, 6-Me (11)-108 Cl 4-Cl, 6-Et (11)-109 Cl 4-Cl,6-c-Pr (11)-110 Cl 4-Cl, 6-OCF3 (11)-111 Cl 4-Cl, 6-Br (11)-112 Cl 4-Br,6-Br (11)-113 Cl 4-Br, 6-OCF3 (11)-114 Cl 4-F, 6-F (11)-115 Cl 4-OMe,6-Et (11)-116 Br 4-Me, 6-Me (11)-117 Br 4-Me, 6-Et (11)-118 Br 4-Me,6-Br (11)-119 Br 4-Cl, 6-OCF3 (11)-120 Br 4-Br, 6-OCF3

TABLE 30 No R2 R3 (12)-1 H H (12)-2 H Me (12)-3 H Et (12)-4 H n-Pr(12)-5 H i-Pr (12)-6 H CH2CH2OMe (12)-7 H CH2CH2OEt (12)-8 H CH2Ph(12)-9 Me H (12)-10 Me Me (12)-11 Me Et (12)-12 Me n-Pr (12)-13 Me i-Pr(12)-14 Me CH2CH2OMe (12)-15 Me CH2CH2OEt (12)-16 Me CH2Ph (12)-17 Et H(12)-18 Et Me (12)-19 Et Et (12)-20 Et n-Pr (12)-21 Et i-Pr (12)-22 EtCH2CH2OMe (12)-23 Et CH2CH2OEt (12)-24 Et CH2Ph (12)-25 n-Pr H (12)-26n-Pr Me (12)-27 n-Pr Et (12)-28 n-Pr n-Pr (12)-29 n-Pr i-Pr (12)-30 n-PrCH2CH2OMe (12)-31 n-Pr CH2CH2OEt (12)-32 n-Pr CH2Ph

TABLE 31 No R2 R3 (12)-33 i-Pr H (12)-34 i-Pr Me (12)-35 i-Pr Et (12)-36i-Pr n-Pr (12)-37 i-Pr i-Pr (12)-38 i-Pr CH2CH2OMe (12)-39 i-PrCH2CH2OEt (12)-40 i-Pr CH2Ph (12)-41 Ph H (12)-42 Ph Me (12)-43 Ph Et(12)-44 Ph n-Pr (12)-45 Ph i-Pr (12)-46 Ph CH2CH2OMe (12)-47 PhCH2CH2OEt (12)-48 Ph CH2Ph (12)-49 4-F—Ph H (12)-50 4-F—Ph Me (12)-514-F—Ph Et (12)-52 4-F—Ph n-Pr (12)-53 4-F—Ph i-Pr (12)-54 4-F—PhCH2CH2OMe (12)-55 4-F—Ph CH2CH2OEt (12)-56 4-F—Ph CH2Ph (12)-57 3-CF3—PhH (12)-58 3-CF3—Ph Me (12)-59 3-CF3—Ph Et (12)-60 3-CF3—Ph n-Pr (12)-613-CF3—Ph i-Pr (12)-62 3-CF3—Ph CH2CH2OMe (12)-63 3-CF3—Ph CH2CH2OEt(12)-64 3-CF3—Ph CH2Ph (12)-65 2-Me—Ph H (12)-66 2-Me—Ph Me (12)-672-Me—Ph Et (12)-68 2-Me—Ph n-Pr (12)-69 2-Me—Ph i-Pr (12)-70 2-Me—PhCH2CH2OMe (12)-71 2-Me—Ph CH2CH2OEt (12)-72 2-Me—Ph CH2Ph

TABLE 32 No. R2 R3 R5 (13)-1 H H Me (13)-2 H H Ph (13)-3 H H 4-Me—Ph(13)-4 H Me Me (13)-5 H Me Ph (13)-6 H Me 4-Me—Ph (13)-7 H Et Me (13)-8H Et Ph (13)-9 H Et 4-Me—Ph (13)-10 H n-Pr Me (13)-11 H n-Pr Ph (13)-12H n-Pr 4-Me—Ph (13)-13 H i-Pr Me (13)-14 H i-Pr Ph (13)-15 H i-Pr4-Me—Ph (13)-16 H CH2CH2OMe Me (13)-17 H CH2CH2OMe Ph (13)-18 HCH2CH2OMe 4-Me—Ph (13)-19 H CH2CH2OEt Me (13)-20 H CH2CH2OEt Ph (13)-21H CH2CH2OEt 4-Me—Ph (13)-22 H CH2Ph Me (13)-24 H CH2Ph Ph (13)-24 HCH2Ph 4-Me—Ph (13)-25 Me H Me (13)-26 Me H Ph (13)-27 Me H 4-Me—Ph(13)-28 Me Me Me (13)-29 Me Me Ph (13)-30 Me Me 4-Me—Ph (13)-31 Me Et Me(13)-32 Me Et Ph (13)-33 Me Et 4-Me—Ph (13)-34 Me n-Pr Me (13)-35 Men-Pr Ph (13)-36 Me n-Pr 4-Me—Ph

TABLE 33 No. R2 R3 R5 (13)-37 Me i-Pr Me (13)-38 Me i-Pr Ph (13)-39 Mei-Pr 4-Me—Ph (13)-40 Me CH2CH2OMe Me (13)-41 Me CH2CH2OMe Ph (13)-42 MeCH2CH2OMe 4-Me—Ph (13)-43 Me CH2CH2OEt Me (13)-44 Me CH2CH2OEt Ph(13)-45 Me CH2CH2OEt 4-Me—Ph (13)-46 Me CH2Ph Me (13)-47 Me CH2Ph Ph(13)-48 Me CH2Ph 4-Me—Ph (13)-49 Et H Me (13)-50 Et H Ph (13)-51 Et H4-Me—Ph (13)-52 Et Me Me (13)-53 Et Me Ph (13)-54 Et Me 4-Me—Ph (13)-55Et Et Me (13)-56 Et Et Ph (13)-57 Et Et 4-Me—Ph (13)-58 Et n-Pr Me(13)-59 Et n-Pr Ph (13)-60 Et n-Pr 4-Me—Ph (13)-61 Et i-Pr Me (13)-62 Eti-Pr Ph (13)-63 Et i-Pr 4-Me—Ph (13)-64 Et CH2CH2OMe Me (13)-65 EtCH2CH2OMe Ph (13)-66 Et CH2CH2OMe 4-Me—Ph (13)-67 Et CH2CH2OEt Me(13)-68 Et CH2CH2OEt Ph (13)-69 Et CH2CH2OEt 4-Me—Ph (13)-70 n-Pr H Me(13)-71 n-Pr H Ph (13)-72 n-Pr H 4-Me—Ph (13)-73 n-Pr Me Me (13)-74 n-PrMe Ph (13)-75 n-Pr Me 4-Me—Ph (13)-76 n-Pr Et Me (13)-77 n-Pr Et Ph(13)-78 n-Pr Et 4-Me—Ph

TABLE 34 No. R2 R3 R5 (13)-79 n-Pr n-Pr Me (13)-80 n-Pr n-Pr Ph (13)-81n-Pr n-Pr 4-Me—Ph (13)-82 n-Pr i-Pr Me (13)-83 n-Pr i-Pr Ph (13)-84 n-Pri-Pr 4-Me—Ph (13)-85 n-Pr CH2CH2OMe Me (13)-86 n-Pr CH2CH2OMe Ph (13)-87n-Pr CH2CH2OMe 4-Me—Ph (13)-88 n-Pr CH2CH2OEt Me (13)-89 n-Pr CH2CH2OEtPh (13)-90 n-Pr CH2CH2OEt 4-Me—Ph (13)-91 n-Pr CH2Ph Me (13)-92 n-PrCH2Ph Ph (13)-93 n-Pr CH2Ph 4-Me—Ph (13)-94 i-Pr H Me (13)-95 i-Pr H Ph(13)-96 i-Pr H 4-Me—Ph (13)-97 i-Pr Me Me (13)-98 i-Pr Me Ph (13)-99i-Pr Me 4-Me—Ph (13)-100 i-Pr Et Me (13)-101 i-Pr Et Ph (13)-102 i-Pr Et4-Me—Ph (13)-103 i-Pr n-Pr Me (13)-104 i-Pr n-Pr Ph (13)-105 i-Pr n-Pr4-Me—Ph (13)-106 i-Pr i-Pr Me (13)-107 i-Pr i-Pr Ph (13)-108 i-Pr i-Pr4-Me—Ph (13)-109 i-Pr CH2CH2OMe Me (13)-110 i-Pr CH2CH2OMe Ph (13)-111i-Pr CH2CH2OMe 4-Me—Ph (13)-112 i-Pr CH2CH2OEt Me (13)-113 i-PrCH2CH2OEt Ph (13)-114 i-Pr CH2CH2OEt 4-Me—Ph (13)-115 i-Pr CH2Ph Me(13)-116 i-Pr CH2Ph Ph (13)-117 i-Pr CH2Ph 4-Me—Ph (13)-118 Ph H Me(13)-119 Ph H Ph (13)-120 Ph H 4-Me—Ph

TABLE 35 No. R2 R3 R5 (13)-121 Ph Me Me (13)-122 Ph Me Ph (13)-123 Ph Me4-Me—Ph (13)-124 Ph Et Me (13)-125 Ph Et Ph (13)-126 Ph Et 4-Me—Ph(13)-127 Ph n-Pr Me (13)-128 Ph n-Pr Ph (13)-129 Ph n-Pr 4-Me—Ph(13)-130 Ph i-Pr Me (13)-131 Ph i-Pr Ph (13)-132 Ph i-Pr 4-Me—Ph(13)-133 Ph CH2CH2OMe Me (13)-134 Ph CH2CH2OMe Ph (13)-135 Ph CH2CH2OMe4-Me—Ph (13)-136 Ph CH2CH2OEt Me (13)-137 Ph CH2CH2OEt Ph (13)-138 PhCH2CH2OEt 4-Me—Ph (13)-139 Ph CH2Ph Me (13)-140 Ph CH2Ph Ph (13)-141 PhCH2Ph 4-Me—Ph (13)-142 4-F—Ph H Me (13)-143 4-F—Ph H Ph (13)-144 4-F—PhH 4-Me—Ph (13)-145 4-F—Ph Me Me (13)-146 4-F—Ph Me Ph (13)-147 4-F—Ph Me4-Me—Ph (13)-148 4-F—Ph Et Me (13)-149 4-F—Ph Et Ph (13)-150 4-F—Ph Et4-Me—Ph (13)-151 4-F—Ph n-Pr Me (13)-152 4-F—Ph n-Pr Ph (13)-153 4-F—Phn-Pr 4-Me—Ph (13)-154 4-F—Ph i-Pr Me (13)-155 4-F—Ph i-Pr Ph (13)-1564-F—Ph i-Pr 4-Me—Ph (13)-157 4-F—Ph CH2CH2OMe Me (13)-158 4-F—PhCH2CH2OMe Ph (13)-159 4-F—Ph CH2CH2OMe 4-Me—Ph (13)-160 4-F—Ph CH2CH2OEtMe (13)-161 4-F—Ph CH2CH2OEt Ph (13)-162 4-F—Ph CH2CH2OEt 4-Me—Ph

TABLE 36 No. R2 R3 R5 (13)-163 4-F—Ph CH2Ph Me (13)-164 4-F—Ph CH2Ph Ph(13)-165 4-F—Ph CH2Ph 4-Me—Ph (13)-166 3-CF3—Ph H Me (13)-167 3-CF3—Ph HPh (13)-168 3-CF3—Ph H 4-Me—Ph (13)-169 3-CF3—Ph Me Me (13)-170 3-CF3—PhMe Ph (13)-171 3-CF3—Ph Me 4-Me—Ph (13)-172 3-CF3—Ph Et Me (13)-1733-CF3—Ph Et Ph (13)-174 3-CF3—Ph Et 4-Me—Ph (13)-175 3-CF3—Ph n-Pr Me(13)-176 3-CF3—Ph n-Pr Ph (13)-177 3-CF3—Ph n-Pr 4-Me—Ph (13)-1783-CF3—Ph i-Pr Me (13)-179 3-CF3—Ph i-Pr Ph (13)-180 3-CF3—Ph i-Pr4-Me—Ph (13)-181 3-CF3—Ph CH2CH2OMe Me (13)-182 3-CF3—Ph CH2CH2OMe Ph(13)-183 3-CF3—Ph CH2CH2OMe 4-Me—Ph (13)-184 3-CF3—Ph CH2CH2OEt Me(13)-185 3-CF3—Ph CH2CH2OEt Ph (13)-186 3-CF3—Ph CH2CH2OEt 4-Me—Ph(13)-187 3-CF3—Ph CH2Ph Me (13)-188 3-CF3—Ph CH2Ph Ph (13)-189 3-CF3—PhCH2Ph 4-Me—Ph (13)-190 2-Me—Ph H Me (13)-191 2-Me—Ph H Ph (13)-1922-Me—Ph H 4-Me—Ph (13)-193 2-Me—Ph Me Me (13)-194 2-Me—Ph Me Ph (13)-1952-Me—Ph Me 4-Me—Ph (13)-196 2-Me—Ph Et Me (13)-197 2-Me—Ph Et Ph(13)-198 2-Me—Ph Et 4-Me—Ph (13)-199 2-Me—Ph n-Pr Me (13)-200 2-Me—Phn-Pr Ph (13)-201 2-Me—Ph n-Pr 4-Me—Ph (13)-202 2-Me—Ph i-Pr Me (13)-2032-Me—Ph i-Pr Ph (13)-204 2-Me—Ph i-Pr 4-Me—Ph

TABLE 37 No. R2 R3 R5 (13)-205 2-Me—Ph CH2CH2OMe Me (13)-206 2-Me—PhCH2CH2OMe Ph (13)-207 2-Me—Ph CH2CH2OMe 4-Me—Ph (13)-208 2-Me—PhCH2CH2OEt Me (13)-209 2-Me—Ph CH2CH2OEt Ph (13)-210 2-Me—Ph CH2CH2OEt4-Me—Ph (13)-211 2-Me—Ph CH2Ph Me (13)-212 2-Me—Ph CH2Ph Ph (13)-2132-Me—Ph CH2Ph 4-Me—Ph

TABLE 38 No. R10 R11 (14)-1 H H (14)-2 H Me (14)-3 H Et (14)-4 H i-Pr(14)-5 H i-Bu (14)-6 H Ph (14)-7 Me Ph (14)-8 Me i-Bu (14)-9 Me Me(14)-10 Et Ph (14)-11 —(CH2)5— (14)-12 —(CH2)4—

TABLE 39 No. R3 R10 R11 (15)-1 Me H H (15)-2 Me H Me (15)-3 Me H Et(15)-4 Me H i-Pr (15)-5 Me H Ph (15)-6 Me Me Ph (15)-7 Me Me Et (15)-8Me Me i-Bu (15)-9 Me —(CH2)5— (15)-10 Et H H (15)-11 Et H Me (15)-12 EtH Et (15)-13 Et H i-Pr (15)-14 Et H Ph (15)-15 Et Me Ph (15)-16 Et Me Et(15)-17 Et Me i-Bu (15)-18 Et —(CH2)5— (15)-19 n-Pr H H (15)-20 n-Pr HMe (15)-21 n-Pr H Et (15)-22 n-Pr H i-Pr (15)-23 n-Pr H Ph (15)-24 n-PrMe Ph (15)-25 n-Pr Me Et (15)-26 n-Pr Me i-Bu (15)-27 n-Pr —(CH2)5—

TABLE 40 No. (Z5)m R3 R10 R11 (16)-1 2-Et, 4-Et, 6-Et H H H (16)-2 2-Et,4-Et, 6-Et H H Ph (16)-3 2-Et, 4-Et, 6-Et H Me Ph (16)-4 2-Et, 4-Et,6-Et H Me Et (16)-5 2-Et, 4-Et, 6-Et H H i-Pr (16)-6 2-Et, 4-Et, 6-Et MeH Ph (16)-7 2-Et, 4-Et, 6-Et Me —(CH2)5— (16)-8 2-Et, 4-Et, 6-Et Me MeMe (16)-9 2-Et, 4-Et, 6-Et Me H Et (16)-10 2-Et, 4-Et, 6-Et Me Me Ph(16)-11 2-Et, 5-(4-Cl—Ph) H H H (16)-12 2-Et, 5-(4-Cl—Ph) H H Ph (16)-132-Et, 5-(4-Cl—Ph) H Me Ph (16)-14 2-Et, 5-(4-Cl—Ph) H Me (16)-15 2-Et,5-(4-Cl—Ph) H H i-Pr (16)-16 2-Et, 5-(4-Cl—Ph) Me H Ph (16)-17 2-Et,5-(4-Cl—Ph) Me —(CH2)4— (16)-18 2-Et, 5-(4-Cl—Ph) Me Me Me (16)-19 2-Et,5-(4-Cl—Ph) Me H Et (16)-20 2-Et, 5-(4-Cl—Ph) Me Me Ph

EXAMPLES

Hereinafter, the present invention will be illustrated by followingExamples in more detail, but not limited thereto.

In the Examples, room temperature means usually 10 to 30° C. In columnchromatography, silica gel 60 (spheral, neutral, particle size: 63-210nm, from KANTO CHEMICAL CO., INC.) was used. When a mixed solvent isused as a developing solvent, the mixture ratio by volume of eachsolvent is shown in parentheses. ¹H NMR means proton nuclear magneticresonance, and was measured with JEOL AL-400 (400 Hz) type and BrukerADBANCE400 (400 Hz) type spectrometer using tetramethylsilan as aninternal standard, and chemical shift (δ) was shown by ppm.

The abbreviations used in the Examples mean as follows:

CDCl₃: chloroform-d, DMSO: dimethylsulfoxide, s: singlet, d: doublet, t:triplet, q: quartet, m: multiplet, br.: broad, J: coupling constant, Me:methyl group, Et: ethyl group, n-Pr: n-propyl group, i-Pr: isopropylgroup, c-Pr: cyclopropyl group, and n-Bu: n-butyl group.

Example 1 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazine-3-one((2-34)-(1)-39) (62.8 mg), dimethylsulfoxide (0.5 ml), and 3.8% byweight of aqueous sodium hydroxide solution (0.5 ml) were added under anitrogen atmosphere at room temperature, and stirred at 70° C. for 4hours. Then, to the reaction mixture was added 3.5% by weight ofhydrochloric acid (4 ml) at room temperature, and extracted withtert-butyl methyl ether. The organic layer was concentrated underreduced pressure to give 37.5 mg of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 7.02 (2H, s), 5.28 (1H, br.), 3.75 (3H, s), 2.39-2.23 (10H, m),1.06 (6H, t, J=7.6 Hz)

Example 2 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (51.2 mg), toluene (0.47 ml), water (0.2 ml),tetra-n-butylammonium bromide (49.9 mg), and sodium hydroxide (54.3 m)were added under a nitrogen atmosphere at room temperature, and stirredat 120° C. for 4 hours. Then, the organic layer was removed. 3.5% byweigh of hydrochloric acid (4 ml) was added to the mixture at roomtemperature, and extracted with tert-butyl methyl ether. Then, theorganic layer was concentrated under reduced pressure to give 40.8 mg of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 3 Production of5-(n-butoxy)-4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-5) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (0.21 g), 1-butanol1 (4 ml, water (0.1 ml), and sodiumhydroxide (0.20 g) were added under a nitrogen atmosphere at roomtemperature, and stirred at 120° C. for 8 hours. Then, to the reactionmixture was added water at room temperature, and extracted withtert-butyl methyl ether. The resulting organic layer was concentratedunder reduced pressure to give 0.74 g of5-(n-butoxy)-4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-5)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 6.94 (2H, s), 3.72 (3H, s), 3.39 (2H, t, J=6.2 Hz), 2.81 (3H, s),2.47-2.31 (7H, m), 1.41 (2H, tt, J=8.0 Hz, 6.2 Hz), 1.23 (2H, qt, J=8.0Hz, 7.3 Hz), 1.12 (6H, t, J=6.2 Hz), 0.78 (3H, t, J=7.3 Hz)

Example 4 Production of5-ethoxy-4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-6) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (52.2 mg), ethanol (674.3 mg), and sodium ethoxide(121.8 mg) were added under a nitrogen atmosphere at room temperatureand stirred for 4 hours at 70° C. To the reaction mixture was addedwater (4 ml) at room temperature, and extracted with tert-butyl methylether. The organic layer was concentrated under reduced pressure to give83.6 mg of5-ethoxy-4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-6)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 6.94 (2H, s), 3.72 (3H, s), 3.45 (2H, q, J=7.0 Hz), 2.50-2.31(7H, m), 2.28 (3H, s), 1.14-1.06 (9H, m)

Example 5 Production of2-benzyl-4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-6-methyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (7)-39 in Table 19)

To a 20 ml volume eggplant flask,2-benzyl-4-(2,6-diethyl-4-methylphenyl)-6-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(7)-39) (67.5 mg), dimethylsulfoxide (0.9 ml), distilled water(0.2 ml), and sodium hydroxide (89.6 mg) were added under a nitrogenatmosphere, and stirred at 50° C. for 2 hours. Then, to the resultingmixture was added distilled water (5 ml) and tert-butyl methyl ether (5ml) at room temperature to wash the aqueous layer. Then, the organiclayer was removed, the aqueous layer was neutralized with concentratedsulfuric acid, followed by extracted with toluene. After theconcentration of the extract, the residue was subjected to columnchromatography (hexane: ethyl acetate=3:1) to gave 39.1 mg of2-benzyl-4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-6-methyl-2,3-dihydro-3-pyridazinone((1-4)-(7)-39).

¹H NMR (CDCl₃)

δ ppm: 7.42 (2H, d, J=6.8 Hz), 7.32-2.26 (3H, m), 7.02 (2H, s), 5.32(2H, s), 5.18 (1H, s) 2.36-2.25 (10H, m), 1.0 (6H, t, J=7.6 Hz)

Example 6 Production of ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (A Compound of the Formula(9-a))

To a 3 L volume four-necked flask, magnesium (cutting chip) (35.31 g)and tetrahydrofuran (anhydrous) (600 ml) were added under a nitrogenatmosphere at room temperature. Once starting to stir, the internaltemperature was raised to about 30° C., dibromoethane (25.4 g) was addeddropwise over 20 minutes to the mixture. After the resulting mixture wasstirred for 30 minutes, the internal temperature was raised to about 50°C. To the mixture was added dropwise 2,6-diethyl-4-methylbromobenzene(10-a) (300.18 g) dissolved in tetrahydrofuran (150 ml) over 2 hours.The resulting mixture was stirred at 50° C. for 1 hour and cooled. Tothe mixture was added dropwise diethyl oxalate (192.5 g) at about 0° C.over 15 minutes. The resulting mixture was stirred at room temperaturefor 2 hours. Then, 3.5% by weight of hydrochloric acid (1000 ml) andconcentrated hydrochloric acid (60 ml) were added with cooling. Afterthe organic solvent was removed under reduced pressure, the aqueouslayer was extracted with tert-butyl methyl ether. The organic layer wasconcentrated under reduced pressure to give 320.82 g of ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (9-a).

¹H NMR (CDCl₃)

δ ppm: 6.92 (2H, s), 4.36 (2H, q, J=7.1 Hz), 2.52 (4H, q, J=7.6 Hz),2.34 (3H, s), 1.36 (3H, t, J=7.1 Hz), 1.16 (6H, t, J=7.6 Hz)

Example 7 Production of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide (A Compound of theFormula (12-1) and No. (11)-39 in Table 27)

To a 100 ml volume four-necked flask, methanol (22.91 g) and hydrazinehydrate (1.93 g) were added at room temperature, and cooled. Ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (9-a) (5.01 g) diluted withmethanol (10.02 g) was added dropwise at 1° C. over 5 minutes. Theresulting mixture was stirred at 2° C. for 4 hours, then the mixture wasfiltered. The resulting filtrate was concentrated, added tert-butylmethyl ether (41 g), and washed with brine (14 g). The resulting organiclayer was dried over sodium sulfate, and concentrated under reducedpressure. The residue was subjected to column chromatography (silicagel: 40 g, hexane: ethyl acetate=1:1) to gave 1.88 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39).

¹H NMR (CDCl₃)

δ ppm: 8.13 (1H, br), 6.93 (2H, s), 4.11 (2H, br), 2.45 (4H, q, J=7.5Hz), 2.34 (3H, s), 1.16 (6H, t, J=7.5 Hz)

Example 8 Production of 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetic acid(A Compound of the Formula (8-a))

To a 3 L volume four-necked flask, ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (9-a) (320.82 g) andtetrahydrofuran (600 ml) were added at room temperature and cooled.10.7% by weight of aqueous sodium hydroxide solution (900 ml) was addeddropwise at 10° C. over 2 hours. The resulting mixture was stirred atroom temperature for 1 hour. After the organic solvent was removed underreduced pressure, tert-butyl methyl ether was added to the aqueous layerto wash. After the organic layer was removed, to the aqueous layer wasadded dropwise concentrated hydrochloric acid (180 ml), and extractedwith tert-butyl methyl ether. The organic layer was concentrated underreduced pressure to give 166.55 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetic acid (8-a).

¹H NMR (CDCl₃)

δ ppm: 6.95 (2H, s), 2.49 (4H, q, J=7.5 Hz), 2.35 (3H, s), 1.16 (6H, t,J=7.5 Hz)

Example 9 Production of 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetylChloride (A Compound of the Formula (6-a))

To a 50 ml volume four-necked flask,2-(2,6-diethyl-4-methylphenyl)-2-oxoacetic acid (8-a) (0.94 g), toluene(anhydrous) (3.0 ml) and dimethylformamide (anhydrous) (0.2 m) wereadded under a nitrogen atmosphere and the internal temperature wasraised to about 50° C. Thionyl chloride (0.45 ml) was added thereto andthe resulting mixture was stirred at 50° C. for 2 hours. The mixture wasconcentrated under reduced pressure, and azeotropically distilled withtoluene to give 0.96 g of 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetylchloride (6-a).

¹H NMR (CDCl₃)

δ ppm: 6.96 (2H, s), 2.53 (4H, q, J=7.6 Hz), 2.38 (3H, s), 1.18 (6H, t,J=7.6 Hz)

Example 10 Production of1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine (A Compound of theFormula (5-0-1))

To a 100 ml volume four-necked flask, 1-methylsulfanyl-2-propanone(7-0-1) (19.46 g) and ethanol (20 ml) were added under a nitrogenatmosphere at room temperature and cooled to about 0° C. To the mixture,monomethylhydrazine (14-a) (8.6 ml) was added dropwise and the resultingreaction mixture was stirred at room temperature for one day. Thereaction mixture was concentrated under reduced pressure to give 16.91 gof 1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine (5-0-1).

¹H NMR (CDCl₃)

δ ppm: 4.61 (1H, br), 3.20 (2H, s), 2.95 (3H, s), 2.01 (3H, s), 1.83(3H, s)

Example 11 Production of1-(2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl)-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine(A Compound of the Formula (4-4) and No. (1)-39 in Table 1)

To a 200 ml volume four-necked flask,1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine (5-0-1) (5.0 g),toluene (anhydrous) (9.6 g), and triethylamine (6.97 g) were added undera nitrogen atmosphere at room temperature. To the mixture,2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl chloride (6-a) (9.57 g)dissolved in toluene (28.8 g) was added dropwise at 0° C. over 2 hours,and stirred at room temperature for 2 hours. To the reaction mixture wasadded water (30 ml) at room temperature, and extracted with tert-butylmethyl ether. The organic layer was concentrated under reduced pressureto give 10.96 g of1-(2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl)-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine((4-4)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 6.91 (1.0H, s), 6.89 (1.0H, s), 3.48 (1.5H, s), 3.31 (1H, s),3.21 (1H, s), 3.19 (1.5H, s), 2.67-2.55 (4H, m), 2.32 (1.5H, s), 2.31(1.5H, s), 2.18 (1.5H, s), 2.11 (1.5H, s), 2.05 (1.5H, s), 1.98 (1.5H,s), 1.23-1.16 (6H, m)

Example 12 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine(a compound of the formula (4-4) and No. (1)-39 in Table 1)

To a 20 ml volume two-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred atroom temperature for 22 hours under a nitrogen atmosphere. Additional1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and themixture was further stirred at room temperature for 7 hours. Then, thereaction mixture was concentrated under reduced pressure. After theconcentration, the residue was subjected to column chromatography(hexane: ethyl acetate=1:1) to gave 0.58 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine((4-4)-(1)-39).

Example 13 Production of1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (A Compound of theFormula (5-2-1)

To a 100 ml volume four-necked flask, 1-methylsulfonyl-2-propanone(7-2-1) (4.99 g) and toluene (36.0 g) were added under a nitrogenatmosphere, and added dropwise 40 wt % of aqueous monomethylhydrazinesolution (14-a) (3.96 g) at room temperature. The resulting mixture wasstirred at room temperature for 16 hours, and then added additional 40wt % of aqueous monomethylhydrazine solution (0.35 g). The resultingmixture was stirred for 24 hours, and refluxed with Dean-Stark apparatusunder reduced pressure at the internal temperature of 50° C. Afterrefluxing, the resulting mixture was cooled to 0° C., and filtered togive 3.56 g of 1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(5-2-1).

¹H NMR (CDCl₃)

δ ppm: 3.83 (2H, s), 3.01 (3H, s), 2.90 (3H, s), 1.93 (3H, a)

Reference Production 1 Production of 1-methylsulfonyl-2-propanone (ACompound of the Formula (7-2-1))

To a 3000 ml volume four-necked flask, 1-methylsulfanyl-2-propanone(7-0-1) (100 g), methanol (900 g), and sodium tungstate (VI) dihydrate(31.66 g) were added at room temperature and the internal temperaturewas raised to 50° C. To the mixture, 30% of aqueous hydrogen peroxidesolution (390 ml) was added dropwise over 3.5 hours. Then, the resultingmixture was stirred at room temperature for two days. Sodium thiosulfate(303.3 g) was added under ice-cooling, and extracted with tert-butylmethyl ether (1000 ml) 3 times then chloroform (1000 ml) 2 times. Theorganic layer was concentrated under reduced pressure to give 108.05 gof 1-methylsulfonyl-2-propanone.

¹H NMR (CDCl₃)

δ ppm: 4.05 (2H, s), 3.04 (3H, s), 2.44 (3H, s)

Reference Production 2 Production of 1-methylsulfonyl-2-propanone (ACompound of the Formula (7-2-1))

To a 500 ml volume four-necked flask, sodium sulfite (57.56 g), water(149.35 g), and sodium hydrogen carbonate (43.56 g) were added under anitrogen atmosphere at room temperature, and the internal temperaturewas raised to 50° C. To the mixture, methanesulfonyl chloride (19-a)(30.33 g) was added dropwise over 45 minutes. The resulting mixture wasstirred at 50° C. for 5 hours, and added dropwise concentrated sulfuricacid (5.11 g). The resulting mixture was stirred at 50° C. for 1 hour.Then, the internal temperature was raised to 70° C., and chloroacetone(21-a) (22.55 g) was added dropwise over 10 minutes. The resultingmixture was stirred at 70° C. for 12 hours, extracted with ethyl acetateat 50° C., and concentrated under reduced pressure to give 29.59 g of1-methylsulfonyl-2-propanone.

Example 14 Production of 1-[2-(2,6-diethyl4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine is compound of the formula (4-34) and No. (1)-39 in Table 1)

To a 100 ml volume four-necked flask,1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (2.51 g),toluene (anhydrous) (10 ml), acetonitrile (anhydrous) (4.0 ml), andtriethylamine (4.0 ml) were added under a nitrogen atmosphere and cooledto about 1° C. To the mixture,2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl chloride (6-a) (3.44 g)dissolved in toluene1 (5 ml) was added dropwise over 1 hour, followed bythe mixture was stirred at 0° C. for 1.5 hours. Water (30 ml) was addedthereto at room temperature, and then the mixture was extracted withtert-butyl methyl ether. The organic layer was concentrated underreduced pressure to give 5.09 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 6.92 (1.2H, s), 6.91 (0.8H, s), 4.05 (1.2H, s) 3.95 (0.8H, s),3.52 (1.8H, s), 3.27 (1.2H, s), 3.05 (1.8H, s), 2.96 (1.2H, s),2.64-2.54 (4H, m), 2.34 (1.2H, s), 2.33 (3H, s), 2.11 (1.8H, s),1.22-1.17 (6H, m)

Examples 15 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(A Compound of the Formula (18-a))

To a 1000 ml volume four-necked flask,1-methyl-2-(2-propylidene)hydrazine (17-a) (9.61 g), acetonitrile (280ml), and triethylamine (17 ml) were added under a nitrogen atmosphereand cooled to about 1° C. To the mixture,2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl chloride (6-a) (27.12 g)dissolved in acetonitrile (77 ml) was added dropwise over 30 minutes.

After stirring at room temperature for 1 hour, the reaction mixture wasconcentrated under reduced pressure. Acetone (300 ml) was added, theprecipitated crystal was filtered out, and the filtrate was concentratedunder reduced pressure. The residue was subjected to columnchromatography (hexane: acetone=3:1) to give 21.41 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(18-a).

¹H NMR (CDCl₃)

δ ppm: 6.90 (1.2H, s), 6.88 (0.8H, s), 3.45 (1.2H, s), 3.14 (1.8H, s),2.67-2.56 (4H, m), 2.32 (1.2H, s), 2.31 (1.8H, s), 2.14 (1.2H, s), 2.03(1.8H, s), 2.02 (1.8H, s), 1.86 (1.2H, s), 1.23-1.17 (6H, m)

Example 16 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine (ACompound of the Formula (12-2) and No. (11)-39 in Table 27)

To a 500 ml volume four-necked flask,1-[(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(18-a) (21.41 g) and tetrahydrofuran (150 ml) were added under anitrogen atmosphere at room temperature. To the mixture, 10% by weightof hydrochloric acid (29.23 g) was added dropwise over 5 minutes, andstirred at room temperature for 1 hour. Then, the reaction mixture wasconcentrated under reduced pressure. To the residue was added water (60ml), and extracted with tert-butyl methyl ether. The organic layer wasconcentrated under reduced pressure, and added hexane (50 ml). Theprecipitated crystal was collected by filtration and dried to give 12.70g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39).

¹H NMR (CDCl₃)

δ ppm: 6.91 (2H, s), 4.60 (1.2H, s), 3.96 (0.8H, s), 3.44 (1.9H, s),3.22 (1.1H, s), 2.66 (1.5H, q, J=7.6 Hz), 2.53 (2.5H, q, J=7.6 Hz), 2.32(3H, s), 1.23-1.18 (6H, m)

Example 17 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (1)-39 in Table 1)

To a 20 ml volume two-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and1-methylsulfonyl-2-propanone (7-2-1) (0.30 g) were added under anitrogen atmosphere and stirred at room temperature for 22 hours. Thereaction mixture was concentrated under reduced pressure. The residuewas subjected to column chromatography (hexane: acetone=3:1) to give0.25 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34-(1)-39).

Example 18 Production of (1-methylsulfonyl-2-propylidene)hydrazine (ACompound of the Formula (5-2-2))

To a 200 ml volume four-necked flask, 1-methylsulfonyl-2-propanone(7-2-1) (10.21 g) and ethanol (50 ml) were added under a nitrogenatmosphere and cooled to 0° C. Hydrazine monohydrate (14-b) (3.9 ml) wasadded dropwise. After stirring at room temperature for 23.5 hours, themixture was concentrated under reduced pressure to give 10.69 g of(1-methylsulfonyl-2-propylidene)hydrazine (5-2-2).

¹H NMR (CDCl₃)

δ ppm: 5.37 (2H, br), 3.83 (2H, s), 2.90 (3H, s), 1.97 (3H, s)

Example 19 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (8)-39 in Table 22)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),1-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-2) (0.14 g), toluene(anhydrous) (0.9 ml), acetonitrile (anhydrous) (0.2 ml), and sodiumhydrogen carbonate (0.14 g) were under a nitrogen atmosphere, and cooledon ice-bath. To the mixture, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetylchloride (6-a) (0.2 g) dissolved in toluene (1.0 ml) was added dropwise.

After the addition, the mixture was stirred for 2 hours. 5.0 ml of waterwas added at room temperature, and extracted with tert-butyl methylether, and then the organic layer was concentrated under reducedpressure. The residue was subjected to column chromatography(chloroform: methanol=9:1) to give 0.06 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine ((4-34)-(8)-39).

¹H NMR (CDCl₃)

δ ppm: 9.89 (1H, s), 6.95 (2H, s), 4.09 (2H, s), 3.01 (3H, s), 2.48 (4H,q, J=7.6 Hz), 2.35 (3H, s), 2.27 (3H, s), 1.17 (6H, t, J=7.6 Hz)

Example 20 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine(A Compound of the Formula (4-4) and No. (8)-39 in Table 22)

To a 200 ml volume four-necked flask,2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39)(6.44 g), tetrahydrofuran (72 ml), and acetic acid (1.65 g) were addedunder a nitrogen atmosphere. 1-methylsulfanyl-2-propanone (7-0-1) (3.12g) was added at room temperature, and the mixture was stirred at roomtemperature for 2 hours. To the reaction mixture was added water (30ml), and extracted with tert-butyl methyl ether. The organic layer wasconcentrated under reduced pressure to give 7.17 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfanyl-2-propylidene)hydrazine((4-4)-(8)-39).

¹H NMR (CDCl₃)

δ ppm: 9.70 (1H, s), 6.93 (2H, s), 3.38 (2H, s), 2.48 (4H, q, J=7.6 Hz),2.34 (3H, s), 2.14 (3H, s), 2.07 (3H, s), 1.16 (6H, t, J=7.5 Hz)

Example 21 Production of1-benzyl-2-(1-methylsulfonyl-2-propylidene)hydrazine monohydrochloride(A Compound of the Formula (5-2-3))

To a 50 ml volume three-necked flask, 1-methylsulfonyl-2-propanone(7-2-1) (2.01 g), methanol (10 ml) and benzylhydrazine monohydrochloride(14-c) (2.56 g) were added under a nitrogen atmosphere at roomtemperature, then additional methanol (10 ml) was added. The resultingreaction mixture was stirred at room temperature for three days, andfiltered to give the primary crystal. The filtrate was concentratedunder reduced pressure, and filtered again to give the crystal. Thecrystal was combined with the primary crystal to give 4.2 g of1-benzyl-2-(1-methylsulfonyl-2-propylidene)hydrazine monohydrochloride(5-2-3). Additionally, the hydrochloride (5-2-3) (0.28 g) was dissolvedin saturated aqueous sodium hydrogen carbonate solution (5.0 ml), andextracted with tert-butyl methyl ether (5.0 ml) 2 times. Then, theorganic layer was concentrated under reduced pressure to give 0.22 g of1-benzyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-3′). NMR dataof Compound (5-2-3′) is shown below.

¹H NMR (CDCl₃)

δ ppm: 7.34-7.23 (5H, m), 5.39 (1H, br), 4.39 (2H, d, J=4.8 Hz), 3.78(2H, s), 2.67 (3H, s), 1.88 (3H, s)

Example 22 Production of1-benzyl-1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (7)-39 in Table 19)

To a 50 ml volume four-necked flask,1-benzyl-2-(1-methylsulfonyl-2-propylidene)hydrazine monohydrochloride(5-2-3) (2.65 g), acetonitrile (9 ml), and triethylamine (2.5 ml) wereadded under a nitrogen atmosphere at room temperature, and cooled toabout 0° C. To the mixture, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetylchloride (6-a) (2.42 g) dissolved in toluene (6 ml) was added dropwiseover 5 minutes.

The resulting mixture was stirred under ice-cooling for 2 hours. Then,the reaction mixture was poured into saturated aqueous sodium hydrogencarbonate solution (60 ml), and extracted with toluene (100 ml) 3 times.Then, the organic layer was washed with saturated aqueous ammoniumchloride solution (100 ml), and concentrated under reduced pressure togive 3.90 g of crude1-benzyl-1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(7)-39). The crude product (1.08 g) was dissolved in ethylacetate (3 ml) and added hexane (7 ml). The resulted precipitate wascollected by filtration to give 0.33 g of1-benzyl-1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(7)-39) as a primary crystal. Further, the filtrate wasconcentrated under reduced pressure followed by a similar procedure togive 0.17 g of the second crystal.

¹H NMR (CDCl₃)

δ ppm: 7.49-7.47 (2H, m), 7.40-7.31 (3H, m), 6.94 (1.6H, s), 6.89 (0.4H,s), 5.06 (1.6H, s), 4.91 (0.4H, s), 3.91 (1.6H, s), 3.90 (0.4H, s), 2.79(2.4H, s), 2.67-2.51 (4.6H, m), 2.34 (2.4H, s), 2.32 (0.6H, s), 2.20(0.6H, s), 1.89 (2.4H, s), 1.26-1.11 (6H, m)

Example 23 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfanyl-2,3-dihydro-3-pyridazinone(a compound of the formula (2-4) and No. (1)-39 in Table 1)

To a 200 ml volume four-necked flask, tetrahydrofuran (anhydrous) (27.0ml) and sodium hydride (1.90 g) were added under a nitrogen atmosphereat about 0° C., and stirred. Then,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine((4-4)-(1)-39) (14.2 g) dissolved in tetrahydrofuran (anhydrous) (45 ml)was added dropwise over 30 minutes, and then the mixture was stirred at0° C. for 2 hours. Then, to the mixture was added water (100 ml) at roomtemperature, and extracted with tert-butyl methyl ether. The organiclayer was concentrated under reduced pressure. The residue was subjectedto column chromatography (hexane: ethyl acetate=4:1) to give 5.45 g of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfanyl-2,3-dihydro-3-pyridazinone.

¹H NMR (CDCl₃)

δ ppm: 6.95 (2H, s), 3.75 (3H, s), 2.44 (3H, s), 2.39-2.32 (2H, m), 1.85(3H, s), 1.13 (6H, t, J=7.5 Hz)

Example 244-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-39 in Table 1)

To a 20 ml volume two-necked flask,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfanyl-2,3-dihydro-3-pyridazinone((2-4)-(1)-39) (0.18 g), chloroform (1.0 ml), and sodium hydrogencarbonate (0.20 g) were added thereto under a nitrogen atmosphere.Meta-chloroperbenzoic acid (0.32 g) was added thereto at roomtemperature, and then the mixture was stirred for 4 hours. Afterstirring, to the reaction mixture was added saturated aqueous sodiumsulfite solution, and extracted with tert-butyl methyl ether. Then, theorganic layer was concentrated under reduced pressure. Then, the residuewas subjected to column chromatography (silica gel 10 g, chloroform:ethyl acetate=15:1) to give 0.12 g of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 7.02 (2H, s), 3.81 (3H, s), 2.73 (3H, s), 2.44 (3H, s), 2.39-2.31(7H, m), 1.15 (6H, t, J=7.5 Hz)

Example 25 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34-(1-39) (104.0 mg), potassium carbonate (60.2 mg) anddimethylformamide (300 mg) were added at room temperature.

After stirring for 22 hours, to the mixture was added water at roomtemperature, and extracted with ethyl acetate. The organic layer wasconcentrated under reduced pressure to give 64.7 mg of a mixture of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39), and5-[(2,6-diethyl-4-methylphenyl)carbonyl]-1,3-dimethyl-4-methylsulfonyl-1H-pyrazole(22)(1H-NMR ratio: ((2-34)-(1)-39)/(22)=7/3).

1H NMR (CDCl₃)

(4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39) δ ppm: 7.02 (2H, s), 3.81 (3H, s), 2.73 (3H, s), 2.44(3H, s), 2.39-2.31 (7H, m), 1.15 (6H, t, J=7.5 Hz)

5-[(2,6-diethyl-4-methylphenyl)carbonyl]-1,3-dimethyl-4-methylsulfonyl-1H-pyrazole(22)

δ ppm: 6.97 (2H, s), 3.48 (3H, s), 3.18 (3H, s), 2.52-2.44 (7H, m), 2.36(3H, s), 1.14 (6H, t, J=7.5 Hz)

Example 26 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34-(1)-39) (201.0 mg), potassium carbonate (115.1 mg), and methanol(757 μl) were added under ice-cooling.

The mixture was stirred under ice-cooling for 3 hours, then added water,and extracted with ethyl acetate. The organic layer was concentratedunder reduced pressure to give 187.5 mg of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 7.02 (2H, s), 3.81 (3H, s), 2.73 (3H, s), 2.44 (3H, s), 2.39-2.31(7H, m), 1.15 (6H, t, J=7.5 Hz)

Example 27 Production of2-benzyl-4-(2,6-diethyl-4-methylphenyl)-6-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (7)-39 in Table 19)

To a 20 ml volume three-necked flask,1-benzyl-1-(2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl)-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(7)-39) (340 mg), toluene (3.0 ml), and potassium carbonate(0.18 g) were added at room temperature, then additional toluene (0.5ml) was added. The resulting mixture was stirred at room temperature for15 hours, then at the internal temperature of about 50° C. for 18 hours.To the resulting mixture, water was added was extracted with tert-butylmethyl ether. The organic layer was concentrated under reduced pressure,purified by column chromatography (hexane: ethyl acetate=5:1), furtherrecrystallized from ethyl acetate to give 67.5 mg of2-benzyl-4-(2,6-diethyl-4-methylphenyl)-6-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(7)-39).

1H NMR (CDCl₃)

δ ppm: 7.42 (2H, d, J=3.7 Hz), 7.32-7.29 (3H, m), 6.99 (2H, s), 5.31(2H, s), 2.73 (3H, s), 2.43 (3H, s), 2.36-2.21 (7H, m), 1.05 (6H, t,J=7.5 Hz)

Example 28 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine(A Compound of the Formula (4-46) and No. (1)-39 in Table 1)

To a 100 ml volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (3.04 g) was placed at room temperature, and addeddropwise a solution of 1,1,1-trifluoro-3-methylsulfanyl-2-propanone(7-0-2) (2.29 g) in toluene (27 g). After para-toluenesulfonic acidmonohydrate (0.028 g) was added, the resulting mixture was stirred underreflux for 45 minutes, and cooled to room temperature. The reactionmixture was poured into water (30 ml), and extracted with ethyl acetate(50 ml) 2 times. The resulting organic layer was dried over magnesiumsulfate, concentrated under reduced pressure, and subjected to silicagel column chromatography (chloroform) to give 2.13 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine((4-46)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 6.92 (1.3H, s), 6.91 (0.7H, s), 3.64 (1H, s), 3.62 (2H, s), 3.57(1.3H, s), 3.32 (0.7H, s), 2.67-2.50 (4H, m), 2.32 (3H, s), 2.20 (2H,s), 2.11 (1H, s), 1.27-1.11 (6H, m)

Example 29 Production of4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-46) and No. (1)-39 in Table 1)

To a 50 ml volume three-necked flask, tetrahydrofuran (anhydrous) (10ml) and potassium t-butoxide (0.17 g) were added at room temperature. Asolution of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine((4-46)-(1)-39) (0.584 g) which was azeotropic-distilled with tolueneone time in tetrahydrofuran (anhydrous) (15 ml) was added dropwise atroom temperature over 8 minutes. The reaction mixture was stirred for 2hours, and added additional potassium t-butoxide (0.166 g). Then, theresulting mixture was stirred for 2 hours. The reaction mixture waspoured into water (70 ml), and extracted with ethyl acetate (50 ml) 2times. The organic layer was washed with saturated brine (30 ml), driedover anhydrous magnesium sulfate, concentrated under reduced pressure,and subjected to silica gel column chromatography (hexane: ethylacetate=30:1 to hexane: ethyl acetate=10:1 to hexane: ethyl acetate=5:1)to give 0.226 g of4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-46)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.00 (2H, s), 3.85 (3H, s), 3.37 (3H, s), 2.45-2.26 (4H, m), 1.86(3H, s), 1.14 (6H, t, J=7.6 Hz)

Example 30 Production of4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-49) and No. (1)-39 in Table 1)

To a 50 ml volume three-necked flask,4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-46)-(1)-39) (0.51 g) and chloroform (12.5 ml) were added at roomtemperature. Sodium hydrogen carbonate (0.46 g) and meta-chlorobenzoicacid (0.48 g) was added and the resulting mixture was stirred at roomtemperature for 3 hours. Then, the reaction mixture was poured intowater (20 ml), added sodium sulfite (0.3 g), and extracted with t-butylmethyl ether (40 ml) 2 times. Then, the organic layer was washed withsaturated brine, dried over anhydrous magnesium sulfate, concentratedunder reduced pressure, and subjected to silica gel columnchromatography (hexane: ethyl acetate=3:1 to hexane: ethyl acetate=1:1)to give 0.461 g of4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-49)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.02 (1H, s), 7.01 (1H, s), 3.92 (3H, s), 2.70 (3H, s), 2.37 (3H,s), 2.53-2.22 (3H, s), 2.17-2.04 (1H, m), 1.20-1.11 (6H, m)

Example 31 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2-methyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-16) and No. (1)-39 in Table 1)

To a 30 ml volume three-necked flask,4-(2,6-diethyl-4-methylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-49)-(1)-39) (0.375 g), N-methylpyrrolidone (3.49 g), water (1.75 g),and sodium hydroxide (0.34 g) were added at room temperature. Theresulting mixture was stirred at 50° C. for 4 hours. Then, the resultingmixture was cooled to room temperature, added 12N hydrochloric acid (1.5ml) and water (15 ml), and extracted with ethyl acetate (30 ml). Theorganic layer was dried over anhydrous magnesium sulfate, concentratedunder reduced pressure, and subjected to silica gel columnchromatography (hexane: ethyl acetate=7:1 to hexane: ethyl acetate=5:1to hexane: ethyl acetate=3:1) to give 0.147 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxyl-2-methyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((1-16)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.06 (2H, s), 5.81 (1H, br), 3.86 (3H, s), 2.37 (3H, s),2.42-2.24 (4H, s), 1.09 (6H, t, J=7.6 Hz)

Example 32 Production of1-([2-(2,4,6-triethylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine(A Compound of the Formula (12-2) and No. (11)-40 in Table 27)

To a 100 ml volume three-necked flask,1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-40) (3.01 g) was added, and to the mixture was addeddropwise a solution of 1,1,1-trifluoro-3-methylsulfanyl-2-propanone(7-0-2) (2.10 g) in toluene (27 g), followed by the addition ofpara-toluenesulfonic acid monohydrate (0.030 g). The resulting mixturewas stirred under reflux for 40 minutes. Then, the reaction mixture wascooled to room temperature, poured into water (30 ml), and extractedwith ethyl acetate (50 ml) 3 times. The resulting organic layer wasdried over magnesium sulfate, concentrated under reduced pressure, andsubjected to silica gel column chromatography (chloroform) to give 2.31g of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine((4-46)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 6.94 (0.7H, s), 6.92 (1.3H, s), 3.64 (1H, s), 3.62 (2H, s), 3.57(1.3H, s), 3.32 (0.7H, s), 2.69-2.52 (6H, m), 2.19 (2H, s), 2.11 (1H,s), 1.27-1.14 (9H, m)

Example 33 Production of4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-46) and No. (1)-40 in Table 1)

To a 200 ml volume four-necked flask, tetrahydrofuran (anhydrous) (60ml) and potassium t-butoxide (0.64 g) were added at room temperature. Asolution of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-2-(1,1,2-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine((4-46)-(1)-40) (2.30 g) which was azeotropic-distilled with toluene onetime in tetrahydrofuran (anhydrous) (60 ml) was added dropwise at roomtemperature over 23 minutes. The reaction mixture was stirred for 30minutes, and then potassium t-butoxide (0.67 g) was added. The resultingreaction mixture was stirred for 30 minutes, poured into water (70 ml),and extracted with ethyl acetate (100 ml) 2 times. The organic layer waswashed with saturated brine (30 ml), dried over anhydrous magnesiumsulfate, concentrated under reduced pressure, purified by silica gelcolumn chromatography (hexane: ethyl acetate=8:1 to hexane: ethylacetate=3:1), recrystallized from hexane, to give 0.282 g of4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-46)-(1)-40). Further, the filtrate was concentrated under reducedpressure, recrystallized from hexane again, and filtered to give 0.406 gof4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-46)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 7.02 (2H, s), 3.85 (3H, s), 2.67 (2H, q, J=7.6 Hz), 2.45-2.28(4H, m), 1.84 (3H, s), 1.27 (3H, t, J=7.6 Hz), 1.15 (6H, t, J=7.6 Hz)

Example 34 Production of4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-49) and No. (1)-40 in Table 1)

To a 100 ml volume four-necked flask,4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfanyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-46)-(1)-40) (0.683 g) and chloroform (24 ml) were added at roomtemperature, and stirred. Sodium hydrogen carbonate (0.597 g), andmeta-chlorobenzoic acid (0.615 g) was added and the resulting mixturewas stirred at room temperature for 4 hours. Then, the reaction mixturewas poured into water (30 ml), added sodium sulfite (0.4 g), andextracted with t-butyl methyl ether (30 ml) 4 times. The combinedorganic layer was washed with saturated brine, dried over anhydrousmagnesium sulfate, concentrated under reduced pressure, and subjected tosilica gel column chromatography (hexane: ethyl acetate=5:1 to hexane:ethyl acetate=1:1) to give 0.692 g of4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-49)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 7.05 (1H, s), 7.02 (1H, s), 3.93 (3H, s), 2.70 (3H, s), 2.78-2.63(2H, m), 2.53-2.04 (4H, m), 1.32-1.23 (3H, m), 1.22-1.11 (6H, m)

Example 35 Production of4-(2,4,6-triethylphenyl)-5-hydroxy-2-methyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-16) and No. (1)-40 in Table 1)

To a 50 ml volume three-necked flask,4-(2,4,6-triethylphenyl)-2-methyl-5-methylsulfinyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((2-49)-(1)-40) (0.692 g), N-methylpyrrolidone (6.40 g), water (3.11 g),and sodium hydroxide (0.626 g) were added at room temperature. Theresulting mixture was stirred at 50° C. for 4 hours. The reactionmixture was cooled to room temperature, added 12N hydrochloric acid (3ml) and water (15 ml), and extracted with ethyl acetate (30 ml) 3 times.The combined organic layer was dried over anhydrous magnesium sulfate,concentrated under reduced pressure, and subjected to silica gel columnchromatography (hexane: ethyl acetate=8:1 to hexane: ethyl acetate=5:1to hexane: ethyl acetate=3:1). Then, the resulting fraction wasconcentrated under reduced pressure, recrystallized from hexane to give0.331 g of4-(2,4,6-triethylphenyl)-5-hydroxy-2-methyl-6-trifluoromethyl-2,3-dihydro-3-pyridazinone((1-16)-(1)-40) on the filter paper.

1H NMR (CDCl₃)

δ ppm: 7.07 (2H, s), 5.99 (1H, br), 3.97 (3H, s), 2.67 (2H, g, J=7.6Hz), 2.43-2.26 (4H, m), 1.27 (2H, t, J=7.6 Hz), 1.09 (6H, t, J=7.6 Hz)

Reference Production 3 Production of 1-methylsulfinyl-2-propanone (ACompound of the formula (7-1-1)

To a 50 ml volume three-necked flask, 1-methylsulfanyl-2-propanone(7-0-1) (24.2 g) was added, and cooled on ice-bath. 33% of aqueoushydrogen peroxide solution (22.6 g) was added dropwise thereto. Then,the mixture was stirred below 5° C. for 3 hours. The resulting reactionmixture was subjected to silica gel column chromatography (ethyl acetateto acetonitrile) to give 24.9 g of 1-methylsulfinyl-2-propanone (7-1-1).

1H NMR (CDCl₃)

δ ppm: 3.70 (1H, d J=16 Hz), 3.86 (1H D J=16 Hz), 2.69 (3H, s), 2.36(3H, s)

Example 36 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfinyl-2-propylidene)hydrazine(A Compound of the Formula (4-19) and No. (1)-39 in Table 1)

To a 50 ml volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (2.0 g), tetrahydrofuran (anhydrous) (5 ml), and1-methylsulfinyl-2-propanone (7-1-1) (1.65 g) were added under anitrogen atmosphere, and stirred at room temperature for 48 hours. Thereaction mixture was concentrated under reduced pressure at roomtemperature. The residue was subjected to silica gel columnchromatography (ethyl acetate to chloroform) to give 0.48 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfinyl-2-propylidene)hydrazine((4-19)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 6.92 (1.1H, s), 6.90 (0.9H, s), 3.87-3.64 (2.0H, m) 3.52 (1.7H,s), 3.23 (1.3H, s), 2.75-2.53 (7.0H, m), 2.32 (3.0H, s), 2.26 (1.3H, s),2.00 (1.7H, s), 1.23-1.17 (6.0H, m)

Example 37 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfinyl-2-propylidene)hydrazine(A Compound of the Formula (4-19) and No. (1)-39 in Table 1)

To a 50 ml volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine((4-4)-(1)-39) (5.60 g) and methanol (14 ml) were added, and cooled onice-bath. 33% of aqueous hydrogen peroxide solution (2.1 g) was addeddropwise thereto. Then, the mixture was stirred at room temperature for12 hours. The reaction mixture was concentrated under reduced pressure.The residue was subjected to silica gel column chromatography (ethylacetate to chloroform) to give 1.95 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfinyl-2-propylidene)hydrazine((4-19)-(1)-39).

Example 38 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfinyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-19) and No. (1)-39 in Table 1)

To a 30 ml volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfinyl-2-propylidene)hydrazine((4-19)-(1)-39) (1.95 g), methanol (1.26 ml), and toluene (5.66 ml) wereadded, and cooled on ice-bath. Lithium hydroxide monohydrate (0.24 g)was added thereto, and the mixture was stirred for 8 hours.

The reaction mixture was added to water, extracted with ethyl acetate 3times. The organic layer was washed with water, and dried over anhydrousmagnesium sulfate. The organic layer was concentrated under reducedpressure. The residue was subjected to silica gel column chromatography(hexane: ethyl acetate=1:1) to give 1.3 g of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfinyl-2,3-dihydro-3-pyridazinone((2-19)-(1)-39).

¹H NMR (CDCl₃)

δ ppm: 7.01 (1.1H, s), 6.97 (0.9H, s), 3.82 (3.0H, s), 2.72 (3.0H, s),2.70 (3.0H, s), 2.46-2.39 (2.0H, m), 2.37 (3.0H, s), 2.20-2.13 (2.0H,m), 1.18-1.13 (6.0H, m)

Example 39 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 50 ml volume three-necked flask,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfinyl-2,3-dihydro-3-pyridazinone((2-19)-(1)-39) (0.60 g), DMSO (2.73 ml), and 10% of aqueoustetra-n-butylammonium hydroxide solution (9.4 g) were added under anitrogen atmosphere, and stirred at 90° C. for 2 hours. The reactionmixture was added to water and hydrochloric acid was added to adjust pHto less than 2. The resulting mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate andconcentrated under reduced pressure. The residue was subjected to silicagel column chromatography (chloroform) to give 0.33 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 40 Production of ethyl 2-(1,3,5-triethylphenyl)-2-oxoacetate (ACompound of the Formula (9-b))

To a 3 L volume four-necked flask, magnesium (cutting chip) (51.4 g) andtetrahydrofuran (anhydrous) (250 ml) were added under a nitrogenatmosphere. After the temperature of the mixture was raised to about 30°C. dibromoethane (17.3 g) was added dropwise. The resulting mixture wasstirred for 30 minutes. To the mixture, 1,3,5-triethylbromobenzene(10-b) (443.5 g) dissolved in tetrahydrofuran (250 ml) was addeddropwise over 2 hours. The mixture was stirred at 50° C. for 1 hour, andcooled to room temperature to give a solution of1,3,5-triethylphenylmagnesium bromide in tetrahydrofuran.

On the other hand, to a 3 L volume four-necked flask, diethyl oxalate(295 g) and tetrahydrofuran (anhydrous) (350 ml) were added under anitrogen atmosphere and cooled on ice-bath. The above mentioned solutionof 1,3,5-triethylphenylmagnesium bromide in tetrahydrofuran was addedthereto with keeping the temperature below 10° C. The resulting mixturewas stirred at room temperature for 2 hours. The pH of the mixture wasadjusted to less than 2 with 20 w/w % of sulfuric acid underice-cooling. The mixture was extracted with toluene. The organic layerwas dried over anhydrous sodium sulfate, and concentrated under reducedpressure to give 495.3 g of ethyl 2-(1,3,5-triethylphenyl)-2-oxoacetate(9-b).

1H NMR (CDCl₃)

δ ppm: 6.94 (2H, s), 4.32-4.40 (2H, m), 2.47-2.79 (6H, m), 1.34-1.41(3H, m), 1.13-1.28 (9H, m)

Example 41 Production of 2-(1,3,5-triethylphenyl)-2-oxoacetic Acid (ACompound of the Formula (8-b))

To a 3 L volume four-necked flask, tetrahydrofuran (750 ml) and ethyl2-(1,3,5-triethylphenyl)-2-oxoacetate (9-b) (261.0 g) were added, andsodium hydroxide (88 g) dissolved in water (237 g) was added dropwisethereto at about 15-20° C. The resulting mixture was stirred at roomtemperature for 1 hour and 30 minutes. The solid was removed bydecantation. The liquid part was concentrated under reduced pressure.The residue was extracted with toluene and water. After the organiclayer was removed, the aqueous layer was washed with toluene. The pH ofthe aqueous layer was adjusted to 1 with dilute sulfuric acid undercooling, and then the aqueous layer was extracted with toluene. Theorganic layer was washed with water, dried over anhydrous magnesiumsulfate, and filtered to remove the insolubles. The filtrate wasconcentrated under reduced pressure to give 214.8 g of2-(1,3,5-triethylphenyl)-2-oxoacetic acid (8-b).

1H NMR (CDCl₃)

δ ppm: 6.97 (2H, s), 2.44-2.75 (6H, m), 1.13-1.28 (9H, m)

Example 42 Production of 2-(1,3,5-triethylphenyl)-2-oxoacetyl Chloride(A Compound of the Formula (6-b))

To a 3 L volume four-necked flask, 2-(1,3,5-triethylphenyl)-2-oxoaceticacid (8-b) (214.8 g), toluene (anhydrous) (740 ml), anddimethylformamide (anhydrous) (22.8 ml) were added under a nitrogenatmosphere. After the temperature was raised to about 50° C. thionylchloride (131 g) was added. The resulting mixture was stirred at 50° C.for 2 hours, and concentrated under reduced pressure to give 204.5 g of2-(1,3,5-triethylphenyl)-2-oxoacetyl chlorine (6-b).

1H NMR (CDCl₃)

δ ppm: 6.98 (2H, s), 2.49-2.74 (6H, m), 1.14-1.29 (9H, m)

Example 43 Production of1-[2-(1,3,5-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (1)-40 in Table 1)

To a 3 L volume four-necked flask,1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (116.0 g),tetrahydrofuran (anhydrous) (600 ml), and triethylamine (98.5 ml) wereadded under a nitrogen atmosphere, and cooled to about 1° C. to themixture, 2-(1,3,5-triethylphenyl)-2-oxoacetyl chloride (6-b) (178.5 g)was added dropwise, and stirred at 0° C. for 1 hour. The reactionmixture was added dropwise to hexane (3 L) at room temperature, andstirred for 1 hour. The precipitated solids were collected byfiltration, washed with hexane (0.5 L×2) and water (0.5 L×6), and driedunder reduced pressure to give 200.9 g of1-[2-(1,3,5-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 6.94 (1.1H, s), 6.93 (0.9H, s), 4.05 (1.2H, s), 3.94 (0.8H, s),3.52 (1.7H, s), 3.27 (1.3H, s), 3.06 (1.7H, s), 2.96 (1.3H, s),2.65-2.55 (6.0H, m), 2.34 (1.3H, s), 2.11 (1.7H, s), 1.25-1.18 (9.0H, m)

Example 44 Production of4-(1,3,5-triethylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula ((2-34) and No. (1)-40) in Table 1)

To a 3 L volume four-necked flask,1-[2-(1,3,5-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-40) (137.9 g), methanol (87 ml), and toluene (400 ml) wereadded under a nitrogen atmosphere, and cooled on ice-bath. Lithiumhydroxide monohydrate (15.2 g) was added thereto, and stirred at 0-5° C.for 6 hours.

Concentrated sulfuric acid (18.7 g) dissolved in water (75 ml) was addedportionwise and keeping the solution temperature below 5° C. (pH 1). Themixture was extracted with toluene, and then the organic layer waswashed with saturated brine, dried over anhydrous magnesium sulfate, andfiltered to remove the insolubles. The filtrate was concentrated underreduced pressure. The resulting solid was washed with hot hexane, anddried under reduced pressure to give 101.0 g of4-(1,3,5-triethylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 7.03 (2H, s), 3.81 (3H, s), 2.73 (3H, s), 2.66 (2H, q, J=8 Hz),2.40 (3H, s), 2.35 (4H, q, J=8 Hz), 1.25 (3H, t, J=8 Hz), 1.15 (6H, t,J=8 Hz)

Example 45 Production of4-(1,3,5-triethylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-40 in Table 1)

To a 1 L volume four-necked flask,4-(1,3,5-triethylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-40) (98.5 g) and N-methyl-2-pyrrolidone (383 ml) were addedat room temperature. Sodium hydroxide (43.5 g) dissolved in water (118ml) and a container washing solution (39 ml of water×2) were added atroom temperature. The mixture was heated to 70±2° C., and stirred for 6hours. To the mixture, toluene (300 ml) and water (500 ml) were added.After the mixture was stirred vigorously, additional toluene (300 ml)was added. The organic layer was removed and ice-water (500 ml) wasadded to the aqueous layer. pH was adjusted to 1-2 with 20 w/w % ofsulfuric acid below 20° C. The precipitated solids were collected byfiltration and washed with water. After air-drying, the solids weredissolved in ethyl acetate, and dried over anhydrous sodium sulfate. Theinsolubles were removed by filtration. The filtrate was concentratedunder reduced pressure. The resulting crude product was purified byrecrystallization (ethyl acetate-hexane) to give 78.0 g of4-(1,3,5-triethylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-40).

1H NMR (CDCl₃)

δ ppm: 7.05 (2H, s), 5.26 (1H, s), 3.77 (3H, s), 2.66 (2H, q, J=8 Hz),2.43-2.26 (7H, m), 1.27 (3H, t, J=8 Hz), 1.07 (6H, t, J=8 Hz)

Reference Production 4 Production of1-(4-fluorophenyl)-2-methylsulfonylethan-1-one (A Compound of theFormula (7-2-3))

To a 1 L volume four-necked flask, sodium methanesulfinate (31.3 g),4-fluorophenacyl chloride (21-b) (48.1 g), and ethanol (300 ml) wereadded under a nitrogen atmosphere, and heated to reflux for 1 hour.After the mixture was cooled to room temperature, water (500 ml) wasadded. The precipitated solids were collected by filtration, washed withwater, and dried. The solids were dissolved in ethyl acetate, dried overanhydrous sodium sulfate, and concentrated under reduced pressure. Theresulting residue was purified by recrystallization (hexane—ethylacetate) acetate) to give 51.9 g of1-(4-fluorophenyl)-2-methylsulfonylethan-1-one (7-2-3).

1H NMR (CDCl₃)

δ ppm: 8.07-8.03 (2H, m), 7.22-7.18 (2H, m), 4.59 (2H, s), 3.15 (3H, s)

Example 46 Production of1-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-2-methylhydrazine (ACompound of the Formula (5-2-4))

To a 50 ml volume three-necked flask,1-(4-fluorophenyl)-2-methylsulfonylethan-1-one (7-2-3) (5.0 g),methylhydrazine (14-a) (1.2 g), and ethanol (17.1 ml) were added under anitrogen atmosphere, and heated to reflux for 4 hours. After the mixturewas cooled, the precipitated solid was removed by filtration. Thefiltrate was concentrated under reduced pressure. To the residue wasadded hot hexane to be dissolved. The mixture was left to cool. Then,the precipitated crystals were collected by filtration, washed, anddried under reduced pressure. The crystal was purified byrecrystallization (methanol) to give 1.8 g of1-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-2-methylhydrazine(5-2-4).

1H NMR (CDCl₃)

δ ppm: 7.69-7.66 (2H, m), 7.10-7.04 (2H, m), 6.65 (1H, br s), 4.45 (2H,s), 3.12 (3H, s), 2.91 (3H, s)

Example 47 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-1-methylhydrazine(A Compound of the Formula (4-64) and No. (1)-39 in Table 1)

To a 30 ml volume two-necked flask,1-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-2-methylhydrazine(5-2-4) (0.90 g) and anhydrous tetrahydrofuran (5 ml) were added under anitrogen atmosphere, and added triethylamine (0.37 g) under cooling. Tothe mixture, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl chloride (6-a)(0.88 g) was added dropwise below 0° C., and stirred under ice-coolingfor 2 hours. The reaction mixture was added to water, and extracted withtert-butyl methyl ether. The organic layer was washed with saturatedbrine, dried over anhydrous sodium sulfate, and concentrated underreduced pressure. The residue was purified by silica gel columnchromatography (tert-butyl methyl ether) to give 1.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-1-methylhydrazine((4-64)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.61-7.57 (2H, m), 7.21-7.12 (2H, m), 6.96 (1.6H, s), 6.88 (0.4H,s), 4.41 (0.4H, s), 4.20 (1.6H, s), 2.99 (0.6H, s), 2.98 (2.4H, s), 2.93(0.6H, s), 2.86 (2.4H, s), 2.70 (3.2H, q, J=7.5 Hz), 2.60 (0.8H, q,J=7.9 Hz), 2.34 (2.4H, s), 2.31 (0.6H, s), 1.25-1.21 (6.0H, m)

Example 48 Production of4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-2-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-64) and No. (1)-39 in Table 1)

To a 10 ml volume two-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-[1-(4-fluorophenyl)-2-methylsulfonylethylidene]-1-methyl-2-oxoacetohydrazide((4-64)-(1)-39) (0.66 g) and methanol (2.5 ml) were added under anitrogen atmosphere. To the mixture, lithium hydroxide monohydrate (62mg) was added under cooling on −5° C. bath, and stirred underice-cooling for 4 hours. After cold dilute hydrochloric acid was addedunder ice-cooling, the mixture was added to cold water, and extractedwith ethyl acetate 3 times. The organic layers were washed withsaturated brine, dried over anhydrous sodium sulfate, and concentratedunder reduced pressure. The residue was subjected to columnchromatography (hexane: ethyl acetate=3:1) to give 0.31 g of4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-2-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-64)-(1)-39) and 0.12 mg of5-[(2,6-diethyl-4-methylphenyl)carbonyl]-3-(4-fluorophenyl)-1-methyl-4-methylsulfonyl-1H-pyrazole(22-b).

4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-2-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-64)-(1)-39)

1H NMR (CDCl₃)

δ ppm: 7.61-7.56 (2H, m), 7.19-7.14 (2H, m), 7.05 (2H, s), 3.89 (3H, s),2.50-2.37 (7H, m), 2.33 (3H, s), 1.19 (6H, t, J=7 Hz)

5-[(2,6-diethyl-4-methylphenyl)carbonyl]-3-(4-fluorophenyl)-1-methyl-4-methylsulfonyl-1H-pyrazole(22-b)

1H NMR (CDCl₃)

δ ppm: 7.59-7.54 (2H, m), 7.15-7.09 (2H, m), 7.01 (2H, s), 3.64 (3H, s),3.13 (3H, s), 2.59-2.51 (4H, m), 2.38 (3H, s), 1.17 (6H, t, J=7 Hz)

Example 49 Production of4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-5-hydroxyl-2-methyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-28) and No. (1)-39 in Table 1)

To a 10 ml volume two-necked flask,4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-2-methyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-64)-(1)-39)) (0.28 g) and N-methyl-2-pyrrolidone (1.09 ml) wereadded under a nitrogen atmosphere. An aqueous solution of sodiumhydroxide (0.11 g) in water (0.56 ml) was added and stirred at 70° C.for 3 hours.

After the mixture was cooling, the mixture was added to iced water, andadded hydrochloric acid to adjust pH to 1. The mixture was extractedwith ethyl acetate 3 times. The organic layer was washed with saturatedbrine, dried over anhydrous sodium sulfate, and concentrated underreduced pressure. The residue was subjected to column chromatography(chloroform) to give 0.10 g of4-(2,6-diethyl-4-methylphenyl)-6-(4-fluorophenyl)-5-hydroxy-2-methyl-2,3-dihydro-3-pyridazinone((1-28)-(1)-39).

1H NMR (CDCl₃)

δ ppm: δ: 7.87-7.81 (2H, m), 7.17-7.11 (2H, m), 7.01 (2H, s), 5.43 (1H,s), 3.89 (3H, s), 2.47-2.30 (7H, m), 1.11 (6H, t, J=8 Hz)

Example 50 Production of1-[2-[5-ethyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)-hydrazine(A Compound of the Formula (4-134) and No. (9)-5 in Table 25)

To a 10 ml volume two-necked flask, oxalyl chloride (0.3 g) and toluene(1 ml) were added under a nitrogen atmosphere, and added a solution of5-ethyl-3-[4-(trifluoromethyl)phenyl]-1-H-pyrazole (24-a) (0.5 g) andtriethylamine (0.25 g) in toluene (1 ml) under cooling on ice-bath of−20° C. After the mixture was stirred under ice-cooling for 2 hours, asuspension of 1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(5-2-1) (0.66 g) and triethylamine (1.0 g) in toluene (2 ml) was added,and stirred for 3 hours.

The reaction mixture was added to water, and extracted with toluene 3times. The organic layer was washed with saturated brine, and dried overanhydrous sodium sulfate. After the insolubles were removed byfiltration, the filtrate was concentrated under reduced pressure. Theresidue was subjected to column chromatography (hexane: ethylacetate=5:1 to 2:1) to give 0.27 g of1-[2-[5-ethyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine ((4-134)-(9)-5) and 0.04 g of1-[2-[5-ethyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl]-2-oxoacetyl-1-methylhydrazine(12-9).

1-[2-[5-ethyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-134)-(9)-5)

1H NMR (CDCl₃)

δ ppm: 7.88 (2.0H, d, J=8 Hz), 7.70-7.65 (2.0H, m), 6.68 (0.4H, s), 6.61(0.6H, s), 4.12 (0.8H, s), 3.75 (1.2H, s), 3.54 (1.7H, s), 3.28 (1.3H,s), 3.18-3.07 (3.3H, m), 2.57 (1.7H, s), 2.40 (1.3H, s), 2.34 (1.7H, s),1.41-1.31 (3.0H, m).

1-[2-[5-ethyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl]-2-oxoacetyl]-1-methylhydrazine(12-9)

1H NMR (CDCl₃)

δ ppm: 7.92 (1.4H, d, J=8 Hz), 7.87 (0.6H, d, J=8 Hz), 7.69-7.63 (2.0H,m), 6.60 (0.7H, s), 6.44 (0.3H, s), 3.92 (1.0H, s), 3.33 (2.0H, s),3.18-3.12 (1.6H, m), 2.74 (0.4H, q, J=8 Hz), 1.39-1.32 (3.0H, m).

Reference Production 5 Production of2-(1-methyl-1H-indol-3-yl)-2-oxoacetyl Chloride (A Compound of theFormula (26-a))

To a 100 ml volume three-necked flask, N-methylindole (5.0 g) anddiethylether (35 ml) were added under a nitrogen atmosphere, and addedoxalyl chloride (9.7 g) at less than 5° C. The mixture was stirred underice-cooling for 3 hours, and the precipitated solids were collected byauction filtration, washed with cold diethylether, and dried underreduced pressure to give 6.1 g of 2-(1-methyl-1H-indol-3-yl)-2-oxoacetylchloride (26-a).

1H NMR (CDCl₃)

δ ppm: 8.40-8.38 (1H, m), 8.15 (1H, s), 7.43-7.40 (3H, m), 3.91 (3H, s)

Example 51 Production of1-methyl-1-[2-(1-methyl-1H-indol-3-yl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-203) and No. (13)-28 in Table 32)

To a 50 ml volume three-necked flask,1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (2.22 g)and tetrahydrofuran (anhydrous) (10 ml) were added under a nitrogenatmosphere. To the mixture, 2-(1-methyl-1H-indol-3-yl)-2-oxoacetylchloride (26-a) (3.0 g) was added dropwise under ice-cooling, andstirred for 2 hours. The reaction mixture was added to iced water, andthe precipitated solids were collected by filtration, washed with waterand hexane, and dried under reduced pressure to give 3.4 g of1-methyl-1-[2(1-methyl-1H-indol-3-yl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-203-(13)28).

1H NMR (CDCl₃)

δ ppm: 8.41-8.36 (0.6H, m), 8.22 (0.4H, d, J=7 Hz), 7.95 (0.6H, s), 7.84(0.4H, s), 7.40-7.29 (3.0H, m), 4.10 (1.2H, a), 3.88-3.83 (3.8H, m),3.38 (1.9H, s), 3.36 (1.1H, s), 3.16 (1.9H, s), 2.80 (1.1H, s), 2.31(1.1H, s), 2.21 (1.9H, s)

Example 52 Production of2,6-dimethyl-4-(1-methyl-1H-indol-3-yl)-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-203) and No. (13)-28 in Table 32)

To a 50 ml volume three-necked flask,1-methyl-1-[2-(1-methyl-1H-indol-3-yl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-203)-(13)-28) (2.0 g), methanol (7.59 ml), and toluene (2.31 ml)were added under a nitrogen atmosphere, then added lithium hydroxidemonohydrate (0.24 g) under cooling on ice-bath of −5° C., and stirredfor 2 hours. To the mixture, cold dilute hydrochloric acid was addedunder ice-cooling, and stirred for 5 minutes. Then, the mixture wasadded to ice water. The precipitated solids were collected byfiltration, and dried under reduced pressure to give 1.7 g of2,6-dimethyl-4-(1-methyl-1H-indol-3-yl)-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-203)-(13)-28).

1H NMR (CDCl₃)

δ ppm: 7.57-7.53 (2H, m), 7.39 (1H, d, J=8 Hz), 7.31 (1H, t, J=8 Hz),7.23 (1H, t, J=7 Hz), 3.39 (3H, s), 3.82 (3H, s), 2.72 (3H, s), 2.51(3H, s)

Example 53 Production of5-hydroxy-2,6-dimethyl-4-(1-methyl-1H-indol-3-yl)-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-201) and No. (12)-10 in Table 30)

To a 20 ml volume two-necked flask,2,6-dimethyl-4-(1-methyl-1H-indol-3-yl)-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-203)-(13)-28) (0.30 g), N-methyl-2-pyrrolidone (1.17 ml), and aaqueous solution of sodium hydroxide (0.14 g) in water (0.6 ml) wereadded under a nitrogen atmosphere, and stirred at 70° C. for 2 hours.The reaction mixture was added to iced water, and washed with ethylacetate. The pH of the resulting aqueous layer was adjusted to 5 withcold dilute hydrochloric acid under ice-cooling. The precipitated solidswere collected by filtration, washed with water, and dried to give 0.18g of5-hydroxy-2,6-dimethyl-4-(1-methyl-1H-indol-3-yl)-2,3-dihydro-3-pyridazinone((1-201)-(12)-10).

1H NMR (CDCl₃)

δ ppm: 7.63 (1H, s), 7.43-7.40 (2H, m), 7.32 (1H, t, J=7 Hz), 7.22 (1H,t, J=8 Hz), 5.95 (1H, s), 3.89 (3H, s), 3.78 (3H, s), 2.37 (3H, s)

Reference Production 6 Production of Ethyl2-(3-methylpyridin-2-yl)-2-oxoacetate (A Compound of the Formula (29-a))

To a 300 ml volume three-necked flask, 2-bromo-3-methylpyridine (28-a)(22.1 g) and diethylether (94 ml) were added under a nitrogenatmosphere, then added n-butyl lithium (2.5M in hexane) (54 ml) dropwisebelow −70° C., and stirred for 2 hours.

On the other hand, to a 500 ml volume three-necked flask, diethyloxalate (39.4 g) and tetrahydrofuran (anhydrous) (66.3 g) were addedunder a nitrogen atmosphere, then added the above mentioned diethyethersolution dropwise at less than −65° C., and stirred for 5 hours. To themixture, water was added at less than −40° C., and extracted with methylt-butyl ether 3 times. The organic layer was washed with saturatedbrine, dried over anhydrous sodium sulfate, and concentrated underreduced pressure. To the residue, methyl t-butyl ether was added undercooling, and then the precipitated crystals were collected byfiltration, washed with cold methyl t-butyl ether, and dried. Theresidue was subjected to column chromatography (hexane: ethylacetate=50:1 to 20:1 to 25:1 to 20:1 to 15:1) to give 11.5 g of ethyl2-(3-methylpyridin-2-yl)-2-oxoacetate (29-a).

1H NMR (CDCl₃)

δ ppm: 8.58 (1H, d, J=5 Hz), 7.66 (1H, d, J=8 Hz), 7.41 (1H, dd, J=8, 5Hz), 4.46 (2H, q, J=7 Hz), 2.67 (3H, s), 1.41 (3H, t, J=7 Hz)

Example 54 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 100 mL volume four-necked flask,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (6.57 g), toluene (16.7 g), benzyltrimethylammoniumchloride (0.16 g), and sodium hydroxide (2.86 g) were added under anitrogen atmosphere, and stirred at 120° C. for 38 hours. Then, water(24.2 g) was added at room temperature. The organic layer was removed,and the aqueous layer was mixed with 3.5 w/w % of hydrochloric acid (20g) at the same temperature, and filtered. The residue was washed withwater (12 g) and dried to give 4.8 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 55 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 100 mL volume four-necked flask,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (6.57 g), toluene (16.7 g), diethylene glycoldimethylether (3.6 g), and sodium hydroxide (2.86 g) were added under anitrogen atmosphere, and stirred at 120° C. for 15 hours. Then, water(24.2 g) was added at room temperature. The organic layer was removed,and then the aqueous layer was mixed with 3.5 w/w % of hydrochloric acid(25 g) at the same temperature, and filtered. The residue was washedwith water (12 g) and dried to give 4.7 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 56 Production of Ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (A Compound of the Formula(9-a))

To a 2 L volume four-necked flask, magnesium (cutting chip) (66.2 g),tetrahydrofuran (anhydrous) (494 g), and toluene (549 g) were addedunder a nitrogen atmosphere at room temperature. After starting to stirthe mixture, dibromoethane (26.9 g) was added dropwise over 10 minutesat about 20° C., and then the internal temperature was raised to 33° C.The resulting mixture was stirred at 30° C. for 20 minutes.2,6-diethyl-4-methylbromobenzene (10-a) (549.0 g) was added dropwisethereto at 40° C. over 1 hour. The resulting mixture was stirred at 50°C. for 51 hours, and diethyl oxalate (389.1 g) dissolved in toluene(550.1 g) was added dropwise thereto at about 0° C. over 1 hour. Theresulting mixture was stirred at about 5° C. for 1 hour. Then, to themixture, 3.5 w/w % of hydrochloric acid (832 g) was added dropwise atthe same temperature. Then the mixture was warmed to room temperature,and the organic layer was separated. The aqueous layer was extractedwith toluene (548.3 g). The organic layers were combined, washed withwater (1098 g) and concentrated under reduced pressure to give 710.8 gof ethyl 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate (9-a).

Reference Production 7 Production of1-(4-methylphenylsulfonyl)-2-propanone (A Compound of the Formula(7-2-4))

To a 100 ml volume three-necked flask, sodium p-toluenesulfinate (20-a)(9.25 g), tetrabutylammonium bromide (1.65 g), toluene (29 g), andchloroacetone (21-a) (5.0 g) were added, and stirred at 65° C. for 1.25hours. To the mixture, water (10 g) was added, and stirred for 4 hours.After the mixture was cooled to room temperature, the organic layer wasseparated, and the aqueous layer was extracted with toluene 2 times. Theorganic layers were combined, washed with saturated brine, dried overanhydrous magnesium sulfate, and concentrated under reduced pressure.The residue was subjected to column chromatography (chloroform: ethylacetate=20:1) to give 9.749 g of 1-(4-methylphenylsulfonyl)-2-propanone(7-2-4).

1H NMR (CDCl₃)

δ ppm: 7.76 (2H, d, J=8 Hz), 7.37 (2H, d, J=8 Hz), 4.14 (2H, s), 2.46(3H, s), 2.41 (3H, s)

Example 57 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-[1-(4-methylphenylsulfonyl)-2-oxoacetyl]-1-methyl-2-[1-(4-methylphenylsulfonyl)-2-propylidene]hydrazine(A Compound of the Formula (4-36) and No. (1)-39 in Table 1)

To a 25 ml volume three-necked flask with Dean-Stark,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (500 mg), toluene (1.75 ml), and1-(4-methylphenylsulfonyl)-2-propanone (7-2-4) (470 mg) were added.Water was removed by azeotropic distillation at 45-50° C. under 100 mmHgfor 1.5 hours. To the mixture, toluene (1.75 ml) was added, and waterwas removed by azeotropic distillation at 60° c. under 120 mmHg for 6hours. The reaction mixture was concentrated under reduced pressure togive 1.109 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-[1-(4-methylphenylsulfonyl)-2-propylidene]hydrazine((4-36)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.84-7.70 (2.0H, m), 7.38-7.14 (2.0H, m), 6.90 (0.9H, s), 6.85(1.1H, s), 4.13 (0.9H, s), 4.06 (1.1H, s), 3.25 (1.4H, s), 3.03 (1.6H,s), 2.55-2.24 (11.6H, m), 2.06 (1.4H, d, J=1 Hz), 1.17 (2.7H, t, J=8Hz), 1.09 (3.3H, t, J=8 Hz)

Example 58 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-(4-methylphenylsulfonyl)-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-36) and No. (1)-39 in Table 1))

To a 10 ml volume two-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-1-methyl-2-oxoacetyl]-2-[1-(4-methylphenylsulfonyl)-2-propylidene]hydrazine((4-36)-(1)-39) (809 mg), toluene (2.3 ml), and methanol (0.5 ml) wereadded. To the mixture, lithium hydroxide monohydrate (77 mg) was addedat 0° C., stirred for 4 hours, and left to stand at 5° C. for 16 hours.The pH of the mixture was adjusted to 1 with 20 w/w % of sulfuric acid.The organic layer was removed, and then the aqueous layer was extractedwith toluene 2 times. The organic layers were combined, washed withsaturated brine, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure. The residue was subjected to columnchromatography (hexane: ethyl acetate=3:1) to give 711 mg of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-(4-methylphenylsulfonyl)-2,3-dihydro-3-pyridazinone((2-36)-(1)-39).

1H NMR (CDCl₃)

δ ppm: 7.32 (2H, d, J=8 Hz), 7.04 (2H, d, J=9 Hz), 6.74 (2H, s), 3.77(3H, s), 2.72 (3H, s), 2.38 (3H, s), 2.30 (3H, s), 2.13-2.05 (4H, m),1.02 (6H, t, J=7 Hz).

Example 59 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 10 ml volume two-necked flask with Dean-Start,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-(4-methylphenylsulfonyl)-2,3-dihydro-3-pyridazinone((2-36)-(1)-39) (699 mg), toluene (2.45 ml), tetrabutylammonium bromide(27 mg), and 48 w/w % of aqueous sodium hydroxide solution (550 mg) wereadded. Water was removed by azeotropic distillation under reflux for 33hours. After the mixture was cooled to room temperature, water wasadded, and the organic layer was removed. To the aqueous layer, 20 w/w %of sulfuric acid was added to adjust pH to 4, and extracted with toluene2 times. The organic layers were combined, and concentrated underreduced pressure. The residue was subjected to column chromatography(hexane: ethyl acetate=5:1) to give 169 mg of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 60 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-phenoxy-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-31) and No. (1)-39 in Table 1)

To a test tube (outside diameter: 21 mm Φ×overall length: 160 mm),phenol (108 mg), toluene (930 mg), and 60% of oily sodium hydride (44mg) were added, and stirred at room temperature for 5 minutes. To themixture,(4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydropyridazin-3-one((2-34)-(1)-39) (299 mg) was added, and stirred at room temperature for1.5 hours and at 100° C. for 1.5 hours. To the mixture,benzyltriethylammonium chloride was added and stirred for 1.5 hours, andthen DMSO (1.1 ml) was added and stirred for 2 hours. After the mixturewas cooled to room temperature, water was added and extracted withtoluene 3 times. The organic layers were combined, washed with 2Naqueous sodium hydroxide solution 3 times, and concentrated underreduced pressure. The residue was subjected to column chromatography(hexane: ethyl acetate=3:1) to give 91 mg of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-phenoxy-2,3-dihydro-3-pyridazinone((1-31)-(1)-39).

1H NMR (CDCl₃)

δ ppm 7.10 (2H, dd, J=8, 8 Hz), 6.93 (1H, dd, J=8, 8 Hz), 6.79 (2H, s),6.61 (2H, d, J=6 Hz), 3.82 (3H, s), 2.40-2.16 (10H, m), 1.06 (6H, t, J=7Hz).

Example 61 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a test-tube (outside diameter: 21 mm Φ×overall length: 160 mm),4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfanyl-2,3-dihydro-3-pyridazinone((2-4)-(1)-39) (300 mg), N-methyl-2-pyrrolidone (875 mg), and sodiummethoxide (410 mg) were added, and stirred at 90° C. for 16 hours. Afterthe mixture was cooled to room temperature, water was added and washedwith toluene. To the aqueous layer, 10 w/w % of hydrochloric acid wasadded to adjust pH to 1, and extracted with toluene 3 times. The organiclayers were combined and concentrated under reduced pressure. Theresidue was subjected to column chromatography (hexane: ethylacetate=3:1) to give 185 mg of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-diethyl-3-pyridazinone((1-4)-(1)-39) and 33 mg of4-(2,6-diethyl-4-methylphenyl)-5-mercapto-2,6-dimethyl-2,3-dihydro-3-pyridazinone(30-a).

4-(2,6-diethyl-4-methylphenyl)-5-mercapto-2,6-dimethyl-2,3-dihydro-3-pyridazinone(30-a).

1H NMR (CDCl₃)

δ ppm: 7.02 (2H, s), 3.76 (3H, s), 3.42 (1H, s), 2.39-2.23 (10H, m),1.11 (6H, t, J=8 Hz).

Example 62 Production of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(A Compound of the Formula (18-b))

To a 500 ml volume four-necked flask,1-methyl-2-(2-propylidene)hydrazine (17-a) (4.96 g), anhydrousacetonitrile (130 ml), and triethylamine (6.354 g) were added under anitrogen atmosphere at room temperature. To the mixture,2-(1,3,5-triethylphenyl)-2-oxoacetyl chloride (6-b) 15.13 g) dissolvedin anhydrous acetonitrile (35 ml) was added dropwise over 12 minutesunder ice-cooling. After the mixture was stirred at room temperature for14 hours, water (200 ml) was added and extracted with ethyl acetate (100ml×3). The organic layers were combined, and dried over anhydrousmagnesium sulfate. After the inorganic salt was removed by filtration,the filtrate was concentrated under reduced pressure to give 14.34 g of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(18-b).

¹H NMR (CDCl₃)

δ ppm: 6.92 (0.67H, s), 6.90 (1.33H, s), 3.45 (1H, s), 3.15 (2H, s),2.77-2.48 (6H, m), 2.14 (1H, s), 2.03 (2H, s), 2.02 (1H, s), 1.87 (2H,s), 1.29-1.12 (9H, m)

Example 63 Production of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methylhydrazine (A Compoundof the Formula (12-2) and No. (11)-40 in Table 27)

To a 100 ml volume four-necked flask,1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylethylidene)hydrazine(18-b) (21.41 g) and ethanol (35 ml) were added under a nitrogenatmosphere, 10 w/w % of hydrochloric acid (14.54 g) was added andstirred at room temperature for 2.5 hours. The reaction mixture wasconcentrated under reduced pressure. To the residue, saturated brine wasadded and extracted with chloroform (120 ml×1, 60 ml×2). The organiclayers were combined, and dried over anhydrous magnesium sulfate. Afterthe inorganic salt was removed by filtration, the filtrate wasconcentrated under reduced pressure to give 19.08 g of a crude product.The crude product was subjected to column chromatography (hexane: ethylacetate=2:1 to 1:1) to give 3.008 g of1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-40).

¹H NMR (CDCl₃)

δ ppm: 6.93 (2H, s), 3.45 (2H, s), 3.24 (1H, s), 2.71-2.51 (6H, m),1.26-1.16 (9H, m)

Example 64 Production of Ethyl2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetate (A Compound of theFormula (9-c))

To a 50 ml volume three-necked flask, magnesium (cutting chip) (296 mg)and anhydrous tetrahydrofuran (6.75 ml) were added under a nitrogenatmosphere. Dibromoethane (95 mg) was added dropwise, and stirred at 50°C. for 30 minutes. To the mixture,2-bromo-4-(4-chlorophenyl)-1-ethylbenzene (10-c) (3.0 g) dissolved intetrahydrofuran (6.75 ml) was added dropwise over 10 minutes, stirredfor 2.5 hours, and cooled to room temperature to give a solution of5-(4-chlorophenyl)-2-ethylphenylmagnesium bromide in tetrahydrofuran.

On the other hand, to a 50 ml volume three-necked flask, diethyl oxalate(1.78 g) and tetrahydrofuran (anhydrous) (6.75 ml) were added under anitrogen atmosphere. To the mixture, the above mentioned solution wasadded dropwise under ice-cooling. After the resulting mixture wasstirred at room temperature for 1 hour, diethyl oxalate (1.78 g) wasadded dropwise, and stirred at room temperature for 30 minutes. The pHof the mixture was adjusted to less than 2 with hydrochloric acid (10w/w %) under ice-cooling, and the mixture was extracted with toluene 3times. The organic layer was washed with dilute hydrochloric acid, waterand brine, and concentrated under reduced pressure. The residue wassubjected to column chromatography (hexane: ethyl acetate=20:1) to giveethyl 2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetate (9-c) (1.65 g).

1H NMR (CDCl₃)

δ ppm: 7.81 (1H, d, J=2 Hz), 7.70 (1H, dd, J=8, 2 Hz), 7.50-7.34 (5H,m), 4.45 (2H, q, J=7 Hz), 2.98 (2H, q, J=7 Hz), 1.42 (3H, t, J=7 Hz),1.28 (3H, q, J=7 Hz)

Example 65 Production of2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetic Acid (A Compound of theFormula (8-c))

To a 50 ml volume three-necked flask, ethyl2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetate (9-c) (1.43 g),methanol (1.9 ml), and potassium hydroxide (600 mg) dissolved in water(3 ml) were added at room temperature, then added methanol (7.6 ml) andwater (3 ml), and stirred at 40° C. for 2 hours. To the mixture wasadded hexane and 2N aqueous potassium hydroxide solution (3 ml), andthen the layers were separated. The aqueous layer was washed with hexaneagain. The organic layers were combined, and extracted with 2N potassiumhydroxide. To the resulting aqueous layer, 10 w/w % of hydrochloric acidwas added to adjust pH to less than 1, and extracted with ethyl acetate3 times. The organic layers were combined, washed with saturated brine,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure to give 1.081 g of2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetic acid (8-c).

1H NMR (CDCl₃)

δ ppm: 8.16 (1H, d, J=2 Hz), 7.73 (1H, dd, J=8, 2 Hz), 7.53-7.41 (4H,m), 7.18 (1H, d, J=8 Hz), 5.59 (1H, br s), 2.94 (2H, q, J=7 Hz), 1.27(3H, t, J=7 Hz)

Example 66 Production of2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl Chloride (A Compound ofthe Formula (6-c))

To a 20 ml volume three-necked flask,2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetic acid (8-c) (1.01 g),toluene (3.5 ml), dimethylformamide (3 drops), and thionyl chloride (624mg) were added under a nitrogen atmosphere, and stirred at 50° C. for 3hours. The mixture was concentrated under reduced pressure, andazeotropic-distilled with toluene 3 times to give 937 mg of2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl chloride (6-c).

1H NMR (CDCl₃)

δ ppm: 7.80 (1H, d, J=2 Hz), 7.77 (1H, dd, J=8, 2 Hz), 7.51-7.43 (5H,m), 3.03 (2H, q, J=7 Hz), 1.29 (3H, t, J=7 Hz).

Example 67 Production of1-[2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (1)-67 in Table 2)

To a 25 ml volume three-necked flask,1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (670 mg),tetrahydrofuran (anhydrous) (2.25 ml), and triethylamine (390 mg) wereadded under a nitrogen atmosphere. To the mixture,2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl chloride (6-c) (937 mg)was added dropwise at 0° C. and stirred for 2 hours. To hexane (15 ml)in a 50 ml volume three-necked flask, the reaction mixture was addeddropwise, stirred for 10 minutes, and filtered. The residue was driedunder reduced pressure, dissolved in ethyl acetate, and filtered again.The filtrate was concentrated under reduced pressure to give 853 mg of1-[2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-67). The filtrate from the first filtration was concentratedunder reduced pressure, the residue was subjected to columnchromatography (hexane: ethyl acetate=1.5:1) to give 240 mg ofadditional1-(2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl)-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-67).

1H NMR (CDCl₃)

δ ppm: 7.84-7.76 (1.0H, m), 7.73-7.64 (1.0H, m), 7.50-7.40 (5.0H, m),4.10 (0.5H, s), 4.05 (0.5H, s), 3.82 (0.3H, s), 3.76 (0.7H, s), 3.47(1.3H, s), 3.30 (0.9H, s), 3.29 (0.8H, s), 3.12-3.00 (3.7H, m), 2.62(1.2H, s), 2.44 (0.8H, s), 2.32 (1.3H, s), 2.23 (1.0H, s), 1.32-1.25(3.0H, m)

Example 68 Production of4-[5-(4-chlorophenyl)-2-ethylphenyl]-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-67 in Table 2)

To a 25 ml volume three-necked flask,1-[2-[5-(4-chlorophenyl)-2-ethylphenyl]-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-67) (853 mg), toluene (1.76 ml), and methanol (1.85 ml) wereadded under a nitrogen atmosphere, then added lithium hydroxidemonohydrate (83 mg) at 0° C. After the mixture was stirred at 0° C. for3 hours, 10 w/w % of hydrochloric acid was added to adjust pH to lessthan 1, and extracted with toluene 3 times. The organic layers werecombined, and concentrated under reduced pressure. The residue wassubjected to column chromatography (hexane: ethyl acetate=3:1) to give349 mg of4-[5-(4-chlorophenyl)-2-ethylphenyl]-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-67) and 66 mg of4-[5-(4-chlorophenyl)-2-ethylphenyl]-5-methoxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(31-a).

1H NMR

-   -   4-[5-(4-chlorophenyl)-2-ethylphenyl]-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone        ((2-34)-(1)-67) δ ppm: 7.63 (1H, dd, J=8, 2 Hz), 7.51-7.45 (3H,        m), 7.39-7.36 (2H, m), 7.27 (1H, d, J=2 Hz), 3.83 (3H, s), 2.73        (3H, s), 2.63 (3H, s), 2.61-2.45 (2H, m), 1.27 (3H, t, J=7 Hz).    -   4-[5-(4-chlorophenyl)-2-ethylphenyl]-5-methoxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone        (31-a)

δ ppm: 7.58-7.48 (3H, m), 7.43-7.33 (4H, m), 3.75 (3H, s), 3.40 (3H, s),2.64-2.45 (2H, m), 2.29 (3H, s), 1.21 (3H, t, J=8 Hz)

Example 69 Production of4-[5-(4-chlorophenyl)-2-ethylphenyl]-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-67 in Table 2)

To a 25 ml volume three-necked flask,4-[5-(4-chlorophenyl)-2-ethylphenyl]-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-67) (290 mg), N-methyl-2-pyrrolidone (890 mg), and aqueoussodium hydroxide solution (410 mg) were added under a nitrogenatmosphere, and stirred at 70° C. for 3 hours. After the reactionmixture was cooled to room temperature, toluene was added and washed.The organic layer was removed. To the resulting aqueous layer, 10 wt %of hydrochloric acid was added to adjust pH to less than 1, andextracted with ethyl acetate 3 times. The organic layers were combined,washed with saturated brine, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure. The residue was subjected to columnchromatography (hexane: ethyl acetate=2:1) to give 157 mg of4-[5-(4-chlorophenyl)-2-ethylphenyl]-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-67).

¹H NMR (CDCl₃)

δ ppm: 7.60 (1H, dd, J=8.2 Hz), 7.49 (3H, d, J=8.0 Hz), 7.38 (2H, d,J=8.0 Hz), 7.32 (1H, d, J=2.0 Hz), 5.43 (1H, s), 3.77 (3H, s), 2.61-2.43(2H, m), 2.34 (3H, s), 1.15 (3H, t, J=8.0 Hz)

Example 70 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine(A Compound of the Formula (4-34) and No. (1)-39 in Table 1)

To a 25 ml volume three-necked flask,1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (1.36 g),tetrahydrofuran (anhydrous) (4.50 ml), and triethylamine (1.22 ml) wereadded under a nitrogen atmosphere, and cooled on ice-bath. To themixture, 2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl chloride (6-a) (2.0g) was added dropwise, and stirred for 2 hours.

On the other hand, to a 50 ml volume three-necked flask, heptane (15 ml)was added. The above mentioned reaction mixture was added dropwise withstirring under ice-cooling. The precipitated crystals were collected byfiltration, washed with heptane 2 times, washed with water 2 times, anddried under reduced pressure to give 2.44 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-39).

Example 71 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-39 in Table 1)

To a 25 mL volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-39) (1.95 g), toluene (4.85 ml), and methanol (1.05 ml) wereadded under a nitrogen atmosphere, then added lithium hydroxidemonohydrate (169 mg) at 0° C. After the mixture was stirred at 0° C. for4 hours, 10 w/w % of hydrochloric acid was added to adjust to pH to lessthan 1, and extracted with toluene 3 times. The organic layers werecombined and concentrated under reduced pressure. The residue wassubjected to column chromatography (hexane: ethyl acetate=3:1) to give1.077 g of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39).

Example 72 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 25 mL volume three-necked flask,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39) (1.71 g), N-methyl-2-pyrrolidone (3.1 ml), and 27 w/w %of aqueous sodium hydroxide solution (2.99 g) were added, and stirred at70° C. for 6 hours. To the mixture was added water (4.0 ml) and toluene(4.6 ml), and then the organic layer was removed. To the resultingaqueous layer, 35 w/w % of hydrochloric acid was added to adjust to pHto less than 1. The precipitated crystals were collected by filtration,washed with water, and dried under reduced pressure to give 1.23 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 73 Production of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (2-34) and No. (1)-39 in Table 1)

To a 25 mL volume three-necked flask with Dean-Stark,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39) (1.01 g), 1-methylsulfonyl-2-propanone (7-2-1) (613mg), and toluene (2.9 ml) were added under a nitrogen atmosphere. Waterwas removed by azeotropic distillation at 60° C. under 100 mmHg for 4hours. The mixture was concentrated under reduced pressure. To theresidue, toluene (1.73 g) and methanol (1.90 ml) were added, thenlithium hydroxide monohydrate (80 mg) was added at 0° C. After themixture was stirred at 0° C. for 4 hours and at 5° C. for 20 hours, 20w/w % of sulfuric acid was added to adjust pH to less than 1. To themixture was added toluene and water, and then the organic layer wasremoved. The aqueous layer was extracted with toluene 2 times. Theorganic layers were combined, and concentrated under reduced pressure togive 1.28 g of4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39).

Example 74 Production of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (1-4) and No. (1)-39 in Table 1)

To a 25 mL volume three-necked flask with Dean-Stark,4-(2,6-diethyl-4-methylphenyl)-2,6-dimethyl-5-methylsulfonyl-2,3-dihydro-3-pyridazinone((2-34)-(1)-39) (1.31 g), toluene (4.55 ml), tetrabutylammonium bromide(61 mg), and 48 w/w % of aqueous sodium hydroxide solution (1.25 g) wereadded under a nitrogen atmosphere. Water was removed by azeotropicdistillation under atmospheric pressure for 22 hours. The reactionmixture was cooled to room temperature, added water, and washed withtoluene. To the resulting aqueous layer, 10 w/w % of hydrochloric acidwas added to adjust pH to less than 3. The precipitated crystals werecollected by filtration, washed with water and dried under reducedpressure to give 0.949 g of4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone((1-4)-(1)-39).

Example 75 Production of4-(2,6-diethyl-4-methylphenyl)-5-methoxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(A Compound of the Formula (31-b))

To a 25 mL volume three-necked flask,1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine((4-34)-(1)-39) (1.00 g) and methanol (3.8 ml) were added under anitrogen atmosphere, and cooled to 0° C. To the mixture was addedtoluene (1.15 g) and lithium hydroxide monohydrate (56 mg). After themixture was stirred at 0° C. for 4 hours and at 5° C. for 16 hours, 48w/w % of aqueous sodium hydroxide solution (445 mg) was added at 5° C.,and stirred at room temperature for 1.5 hours and at 60° C. for 3 hours.To the mixture, water and toluene were added, then 20 w/w % of sulfuricacid was added to adjust pH to less than 1. After the organic layer wasremoved, the aqueous layer was extracted with toluene 2 times. Theorganic layers were combined, washed with saturated brine, andconcentrated under reduced pressure to give 746 mg of4-(2,6-diethyl-4-methylphenyl)-5-methoxy-2,6-dimethyl-2,3-dihydro-3-pyridazinone(31-b).

1H NMR (CDCl₃)

δ ppm: 6.95 (2H, s), 3.72 (3H, s), 3.33 (3H, s), 2.47-2.32 (7H, m), 2.27(3H, s), 1.13 (6H, t, J=8 Hz).

Example 76 Production of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide (A Compound of theFormula (12-1) and No. (11)-39 in Table 27)

To a 100 mL volume three-necked flask, ethyl2-(2,6-diethyl-4-methylphenyl)-2-oxoacetate ((9-a) (10.0 g)) and toluene(35 ml) were added. Hydrazine hydrate (2.13 ml) was added dropwisethereto at 60° C. and the obtained mixture was stirred at 70° C. for 7hours. The reaction mixture was cooled to room temperature, water wasadded thereto and the organic layer was removed. The aqueous layer wasextracted with toluene. The organic layers were combined andconcentrated under reduced pressure to give 9.40 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39).

Example 77 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-phenyl-1-ethylidene)hydrazine(A Compound of the Formula (40-a) and No. (14)-7 in Table 38)

To a 50 mL volume two-necked flask, 3.0 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39), 20ml of THF (anhydrous), 1.73 g of acetophenone and 780 mg of acetic acidwere added under a nitrogen atmosphere, and the mixture was stirred for6 hours under reflux. The reaction mixture was cooled to roomtemperature and concentrated under reduced pressure. Water was added tothe residue and the resultant was extracted with t-butyl methyl ether.The organic layer was concentrated under reduced pressure and hexane wasadded thereto. The precipitated crystals were collected by filtrationand dried to give 3.77 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(1-phenyl-1-ethylidene)hydrazine((40-a)-(14)-7).

1H NMR (CDCl₃)

δ ppm: 9.95 (1H, s), 7.89 (2H, m), 7.41 (3H, m), 6.95 (2H, s), 2.49 (4H,q, J=8 Hz), 2.41 (3H, s), 2.35 (3H, s), 1.18 (6H, t, J=8 Hz).

Example 78 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-phenyl-1-ethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-6 in Table 39)

To a 20 mL volume two-necked flask, 0.50 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39), 10 ml of tetrahydrofuran (anhydrous), 0.27 g ofacetophenone and 130 mg of acetic acid were added under a nitrogenatmosphere, and the mixture was stirred for 6 hours under reflux. Thereaction mixture was cooled to room temperature and concentrated underreduced pressure. Water (60 ml) was added to the residue and theresultant was extracted with t-butyl methyl ether. The organic layer wasconcentrated under reduced pressure and subjected to silica gel columnchromatography (ethyl acetate: chloroform=3:1) to give 0.32 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-phenyl-1-ethylidene)hydrazine((40-b)-(15)-6).

1H NMR (CDCl₃)

δ ppm: 7.84 (0.6H, d, J=6.6 Hz), 7.89 (1.4H, d, J=7.1 Hz), 7.41 (3H, m),6.91 (0.7H, s), 6.87 (1.3H, s), 3.59 (1H, s), 3.27 (2H, s), 2.65 (4H,m), 2.41 (2H, s), 2.32 (1H, s), 2.30 (2H, s), 2.24 (1H, s), 1.23 (2H, t,J=7.5 Hz), 1.19 (4H, t, J=7.5 Hz)

Example 79 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-a) and No. (14)-6 in Table 38)

To a 100 mL volume three-necked flask with Dean-Stark, 9.38 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39), 32ml of toluene and 4.51 g of benzaldehyde were added under a nitrogenatmosphere, and the mixture was subjected to azeotropic dehydrationunder 100 mmHg at 50° C. for 2 hours. The reaction mixture wasconcentrated under reduced pressure to give 12.51 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a)-(14)-6).

1H NMR (CDCl₃)

δ ppm: 9.99 (1H, s), 8.40 (1H, d, J=10 Hz), 7.81-7.77 (2H, m), 7.45-7.40(3H, m), 6.94 (2H, s), 2.50 (4H, q, J=7 Hz), 2.35 (3H, s), 1.17 (6H, t,J=7 Hz).

Example 80 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-5 in Table 39)

To a 25 mL volume three-necked flask, 300 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a)-(14)-6), 1.9 ml of acetone, 386 mg of potassium carbonate and152 mg of dimethyl sulfate were added under a nitrogen atmosphere, andthe mixture was stirred at room temperature for 1.5 hours. Water wasadded to the reaction mixture and the resultant was extracted with ethylacetate three times. The organic layers were combined and dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to column chromatography (hexane: ethylacetate=10:1) to give 261 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5) and 28 mg of methyl2-(2,6-diethyl-4-methylphenyl)-2-oxo-N-(phenylmethylidene)ethanehydrazonate(compound (x-1)).

1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5)

1H NMR (CDCl₃)

δ ppm: 7.81 (1H, s), 7.54-7.51 (2H, m), 7.38-7.33 (3H, m), 6.94 (2H, s),3.47 (3H, s), 2.71 (4H, q, J=7 Hz), 2.33 (3H, s), 1.20 (6H, t, J=7 Hz).

Methyl2-(2,6-diethyl-4-methylphenyl)-2-oxo-N-(phenylmethylidene)ethanehydrazonate

1H NMR (CDCl₃)

δ ppm: 8.67 (1H, s), 7.87-7.83 (2H, m), 7.48-7.45 (3H, m), 6.93 (2H, s),3.90 (3H, s), 2.51 (4H, q, J=7 Hz), 2.34 (3H, s), 1.16 (6H, t, J=7 Hz).

Example 81 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-5 in Table 39)

To a 100 mL volume three-necked flask, 5.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a-(14)-6), 31 ml of methyl isobutyl ketone, 6.43 g of potassiumcarbonate and 1.75 ml of dimethyl sulfate were added and the mixture wasstirred at room temperature for 7.5 hours. Water was added to thereaction mixture, the organic layer was removed and then the aqueouslayer was extracted with 31 ml of methyl isobutyl ketone. The organiclayers were combined, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure to give 0.324 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5)) and 0.324 g of methyl2-(2,6-diethyl-4-methylphenyl)-2-oxo-N-(phenylmethylidene)ethanehydrazonate(X-1).

Example 82 Production of1-[2-(2,6-diethyl)-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-5 in Table 39)

To a 50 mL volume three-necked flask, 7.6 mg of hydrazine hydrate, 2.3ml of toluene, 629 mg of potassium carbonate and 574 mg of dimethylsulfate were added and the mixture was stirred at room temperature for 1hours. The reaction mixture was cooled to 5° C. and 1.6 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a)-(14)-6) solved in 2.3 g of toluene was added thereto. Thereaction mixture was stirred at 5° C. for 31.5 hours. 5 mL of water wasadded and the resultant was neutralized to pH 7 with 20 wt % of sulfuricacid. The organic layer was removed and the aqueous layer was extractedwith toluene two times. The organic layers were combined andconcentrated under reduced pressure to give 1.22 g of a mixture (22:1(GC area %)) of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2,6-diethyl-4-methylphenyl)-2-oxo-N-(phenylmethylidene)ethanehydrazonate(x-1).

Example 83 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-5 in Table 39)

To a 50 mL volume three-necked flask, 1.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a)-(14)-6), 3.5 ml of toluene and 629 mg of potassium carbonatewere added and then, 9.1 mg of N,N-dimethylhydrazine solved in 2.3 ml oftoluene and 577 mg of dimethyl sulfate were added thereto at 5° C. Themixture was stirred at 5° C. for 24 hours, 3 g of water was addedthereto and the organic layer was removed. The aqueous layer wasextracted with 3.5 ml of toluene two times. The organic layers werecombined and concentrated under reduced pressure to give 1.037 g of amixture (19:1 (GC area %)) of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5) and methyl2-(2,6-diethyl-4-methylphenyl)-2-oxo-N-(phenylmethylidene)ethanehydrazonate(x-1)

Example 84 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-5 in Table 39)

To a 25 mL volume two-necked flask, 500 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine((40-a)-(14)-6), 2.3 ml of toluene, 345 mg of dimethyl sulfate and 315mg of potassium carbonate were added and the mixture was stirred at 5°C. for 24 hours. To the reaction mixture, 2 ml of water and 2.3 ml oftoluene were added and the resultant was extracted. Further, the aqueouslayer was extracted with 2.5 ml of toluene two times. The organic layerswere combined, concentrated under reduced pressure and subjected tocolumn chromatography (hexane: ethyl acetate=5:1) to give 411 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5).

Example 85 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine (ACompound of the Formula (12-2) and No. (11)-39 in Table 27)

To a 25 mL volume two-necked flask, 1.47 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5), 5.1 ml of 1,2-dimethoxyethane and 147 mg of 5 wt % Pd—Cwere added. The mixture was stirred under a hydrogen atmosphere at roomtemperature for 8 hours. An unsolved substance was removed by filtrationand washed with 1,2-dimethoxyethane. The filtrates were combined andconcentrated under reduced pressure to give 1.06% g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39).

Example 86 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine (ACompound of the Formula (12-2) and No. (11)-39 in Table 27)

To a test tube (outside diameter 21 mmφ×overall length 160 mm), 100 mgof1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine((40-b)-(15)-5), 0.5 ml of methanol, 10 mg of 10 wt % Pd-c and one dropof concentrated hydrochloric acid were added and the mixture was stirredat 0° C. for 7 hours under hydrogen atmosphere. An unsolved substancewas removed by filtration and washed with methanol. The filtrates werecombined and concentrated under reduced pressure to give 70 m g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39)

Example 87 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(2-methyl-1-propylidene)hydrazine(A Compound of the Formula (40-a) and No. (14)-4 in Table 38)

To a 300 mL volume three-necked flask, 20.0 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39), 76ml of methanol and 12.3 g of isobutylaldehyde were added and the mixturewas stirred at room temperature for 1.5 hours. The reaction mixture wasconcentrated under reduced pressure and then hexane was added thereto.The precipitated crystals were collected by filtration and dried underreduced pressure to give 23.2 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(2-methyl-1-propylidene)hydrazine((40-a)-(14)-4).

Example 88 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine(A Compound of the Formula (40-b) and No. (15)-4 in Table 39)

To a 50 mL volume three-necked flask, 5.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(2-methyl-1-propylidene)hydrazine((40-a)-(14)-4), 19 ml of acetone, 7.19 g of potassium carbonate and2.13 ml of dimethyl sulfate were added and the mixture was stirred atroom temperature for 6 hours. Water and toluene were added to thereaction mixture and the resultant was extracted. Further, aqueous layerwas extracted with toluene two times. The organic layers were combinedand washed with saturated brine, dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The resultant was subjected tocolumn chromatography (hexane:ethyl acetate=6:1 to 2:1) to give 2.99 gof1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine((40-b)-(15)-4) and 0.28 g of methyl2-(2,6-diethyl-4-methylphenyl)-N-(2-methyl-1-propylidene)-2-oxoethanehydrazonate(x-2).

1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine((40-b)-(15)-4)

¹H NMR (CDCl₃)

δ ppm: 7.04 (1H, d, J=5 Hz), 6.90 (2H, s), 3.27 (3H, s), 2.67 (4H, q,J=8 Hz), 2.55-2.42 (1H, m), 2.32 (3H, s), 1.19 (6H, t, J=7 Hz), 1.04(6H, d, J=7 Hz).

methyl2-(2,6-diethyl-4-methylphenyl)-N-(2-methyl-1-propylidene)-2-oxoethanehydrazonate(x-2)

¹H NMR (CDCl₃)

δ ppm: 7.49 (1H, d, J=5 Hz), 6.88 (2H, s), 3.85 (3H, s), 2.59 (4H, q,J=8 Hz), 2.38-2.30 (4H, m), 1.18 (6H, t, J=8 Hz), 0.92 (6H, d, J=7 Hz).

Example 89 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine(a compound of the formula (40-b) and No. (15)-4 in Table 39)

To a 50 mL volume three-necked flask, 5.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(2-methyl-1-propylidene)hydrazine((40-a)-(14)-4), 16 ml of DMF, 7.19 g of potassium carbonate and 2.13 mlof dimethyl sulfate were added and the mixture was stirred at roomtemperature for 2.5 hours. Water and toluene were added to the reactionmixture and the resultant was extracted. Further, aqueous layer wasextracted with toluene two times. The organic layers were combined andwashed with saturated brine, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The resultant was subjected tocolumn chromatography (hexane:ethyl acetate=6:1 to 2:1) to give 3.04 gof1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine((40-b)-(15)-4) and 0.74 g of methyl2-(2,6-diethyl-4-methylphenyl)-N-(2-methyl-1-propylidene)-2-oxoethanehydrazonate(x-2).

Example 90 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine (ACompound of the Formula (12-2) and No. (11)-39 in Table 27)

To a 25 mL volume three-necked flask, 1.0 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(2-methyl-1-propylidene)hydrazine((40-b)-(15)-4), 3.8 ml of methanol and 330 mg of 50 wt % hydroxylamineaqueous solution were added, and the mixture was stirred at 50° C. for2.5 hours and then 60° C. for 14.5 hours. The reaction mixture wasconcentrated under reduced pressure and water and t-butyl methyl etherwere added to the residue. The precipitated crystals were collected byfiltration, washed with hexane and dried to give 0.63 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39).

Example 91 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-propylidenehydrazine (ACompound of the Formula (40-a) and No. (14)-3 in Table 38)

To a 100 mL volume three-necked flask, 10.0 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazine ((12-1)-(11)-39), 38ml of methanol and 6.16 ml of propanal were added, and the mixture wasstirred at room temperature for 2 hours. The reaction mixture wasconcentrated under reduced pressure. The residue was washed with hexaneand dried under reduced pressure to give 9.44 g or1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-propylidenehydrazine((40-a)-(14)-3).

Example 92 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-propylidenehydrazine(A Compound of the Formula (40-b) and No. (15)-1 in Table 39)

To a test tube (outside diameter 21 mmφ×overall length 160 mm), 100 mgof 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39), 380 mg of methanol and 58 μl of propanal were addedand the mixture was stirred at room temperature for 1.5 hours. Water wasadded to the reaction mixture and the resultant was extracted withchloroform three times. The organic layers were combined, dried overanhydrous magnesium sulfate and concentrated under reduced pressure togive 127 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-propylidenehydrazine((40-b)-(15)-3).

1H NMR (CDCl₃)

δ ppm: 7.13 (1H, t, J=5 Hz), 6.90 (2H, s), 3.27 (3H, s), 2.68 (4H, q,J=7 Hz), 2.32 (3H, s), 2.30-2.23 (2H, m), 1.19 (6H, t, J=7 Hz), 1.03(3H, t, J=8 Hz).

Example 93 Production of2-ethylidene-1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]hydrazine (ACompound of the Formula (40-a) and No. (14)-2 in Table 38)

To a 100 mL volume three-necked flask, 10.0 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39), 38ml of methanol and 4.79 ml of acetaldehyde were added and the mixturewas stirred at room temperature for 1 hour. The reaction mixture wasconcentrated under reduced pressure, and the residue was washed withhexane and dried under reduced pressure to give 9.71 g of2-ethylidene-1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]hydrazine((40-a)-(14)-2) as a mixture (5:1) of geometrical isomer.

Example 94 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-ethylidene-1-methylhydrazine(A Compound of the Formula (40-b) and No. (15)-2 in Table 39)

To a test tube (outside diameter 21 mmφ×overall length 160 mm), 100 mgof 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39), 380 mg of methanol and 45 μl of acetaldehyde wereadded and the mixture was stirred at room temperature for 2 hours. Waterwas added to the reaction mixture and the resultant was extracted withchloroform three times. The organic layers were combined, dried overanhydrous magnesium sulfate and concentrated under reduced pressure togive 103 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-ethylidene-1-methylhydrazine((40-b)-(15)-2).

1H NMR (CDCl₃)

δ ppm: 7.12 (1H, q, J=5 Hz), 6.90 (2H, s), 3.26 (3H, s), 2.69 (4H, q,J=7 Hz), 2.32 (3H, s), 1.92 (3H, d, J=5 Hz), 1.20 (6H, t, J=7 Hz).

Example 95 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-methylidenehydrazine (ACompound of the Formula (40-a) and No. (14)-1 in Table 38)

To a 100 mL volume three-necked flask, 10.0 g of2-(2,6-diethyl-4-methylphenyl)-2-oxoacetohydrazide ((12-1)-(11)-39), 38ml of methanol and 6.93 g of 37 wt % formalin aqueous solution wereadded and the mixture was stirred at room temperature for 5 hours.Methanol was added to the reaction mixture and cooled on ice-bath. Theprecipitated crystals were collected by filtration, washed with coolmethanol, and dried under reduced pressure to give 1.22 g of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-methylidenehydrazine((40-a)-(14)-1).

1H NMR (CDCl₃)

δ ppm: 9.44 (1H, s), 6.91 (2H, s), 4.53 (2H, br s), 2.44 (4H, q, J=7Hz), 2.33 (3H, s), 1.13 (6H, t, J=7 Hz).

Example 96 Production of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-methylidenehydrazine(A Compound of the Formula (40-b) and No. (15)-1 in Table 39)

To a test tube (outside diameter 21 mmφ×overall length 160 mm), 100 mgof 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine((12-2)-(11)-39), 380 mg of methanol and 130 μl of 37 wt % formalinaqueous solution were added and the mixture was stirred at roomtemperature for 2.5 hours. Water was added to the reaction mixture andthe resultant was extracted with chloroform three times. The organiclayers were combined, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure to give 97 mg of1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-methylidenehydrazine((40-b)-(15)-1).

1H NMR (CDCl₃)

δ ppm: 6.91 (2H, s), 6.74 (1H, d, J=10 Hz), 6.50 (1H, d, J=10 Hz), 3.28(3H, s), 2.67 (4H, q, J=7 Hz), 2.32 (3H, s), 1.19 (6H, t, J=7 Hz).

The invention claimed is:
 1. A compound of the formula (4A):

wherein the symbols in the formula (4A) are defined as follows: R^(2-4A)represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkylgroup, a (C1-C6 alkylthio)C1-C6 alkyl group, a (C1-C6alkylsulfinyl)C1-C6 alkyl group, a (C1-C6 alkylsulfonyl)C1-C6 alkylgroup, a phenyl group, or a 5- or 6-membered heteroaryl group; whereinthe C1-C6 alkyl group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, the(C1-C6 alkylthio)C1-C6 alkyl group, the (C1-C6 alkylsulfinyl)C1-C6 alkylgroup, and the (C1-C6 alkylsulfonyl)C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent, the phenyl group and the 5- or 6-membered heteroaryl groupmay optionally have one or more substituents selected from Group 2-4A,provided that when they have two or more substituents, then thesubstituents may be same or different; the Group 2-4A consists ofhalogen, a cyano group, a nitro group, a formyl group, a C1-C6 alkylgroup, a C1-C6 alkoxy group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6alkylthio group, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonylgroup, a C1-C6 alkylamino group, a di(C1-C6 alkyl)amino group, a C3-C6cycloalkylamino group, a (C1-C6 alkyl)carbonyl group, a (C3-C6cycloalkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a (C1-C6alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl group, a(C3-C6 cycloalkylamino)carbonyl group, and a tri(C1-C6 alkyl)silylgroup; in the Group 2-4A, the C1-C6 alkyl group, the C1-C6 alkoxy group,the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6alkynyl group, the C3-C6 cycloalkyl group, the C1-C6 alkylthio group,the C1-C6 alkylsulfinyl group, the C1-C6 alkylsulfonyl group, the (C1-C6alkyl)carbonyl group, the (C3-C6 cycloalkyl)carbonyl group, and the(C1-C6 alkoxy)carbonyl group may be optionally substituted with one ormore halogens, provided that when they are substituted with two or morehalogens, then the halogens may be same or different; R^(3-4A)represents hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkylgroup, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C6 cycloalkylgroup, a (C1-C6 alkylthio)C1-C6 alkyl group, a C1-C6 alkylsulfonylgroup, a (C1-C6 alkyl)carbonyl group, a (C1-C6 alkoxy)carbonyl group, a(C1-C6 alkylamino)carbonyl group, a di(C1-C6 alkyl)aminocarbonyl group,a (C3-C6 cycloalkylamino)carbonyl group, a phenyl group, a benzyl group,or a phenylsulfonyl group; wherein the C1-C6 alkyl group, the (C1-C6alkoxy)C1-C6 alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynylgroup, the C3-C6 cycloalkyl group, the (C1-C6 alkylthio)C1-C6 alkylgroup, the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,and the (C1-C6 alkoxy)carbonyl group may be optionally substituted withone or more halogens, provided that when they are substituted with twoor more halogens, then the halogens may be same of different; and thephenyl group, the benzyl group, and the phenylsulfonyl group mayoptionally have one or more substituents selected from Group 3-4A,provided that when they have two or more substituents, then thesubstituents may be same or different; the Group 3-4A consists ofhalogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, and a (C1-C6alkoxy)C1-C6 alkyl group; in the Group 3-4A, the C1-C6 alkyl group, theC1-C6 alkoxy group, and the (C1-C6 alkoxy)C1-C6 alkyl group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; R^(5-4A) represents a C1-C6 alkyl group or a phenylgroup; wherein the C1-C6 alkyl group may be optionally substituted withone or more halogens, provided that when it is substituted with two ormore halogens, then the halogens may be same or different; and thephenyl group may optionally have one or more substituents selected fromGroup 5-4A, provided that when it has two or more substituents, then thesubstituents may be same or different; the Group 5-4A consists ofhalogen, a C1-C6 alkyl group, and a C1-C6 alkoxy group; in the Group5-4A, the C1-C6 alkyl group, and the C1-C6 alkoxy group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; G^(4A) represents a C6-C10 aryl group, a 5- or6-membered heteroaryl group, or an 8- to 10-membered fused heteroarylgroup; wherein the C6-C10 aryl group, the 5- or 6-membered heteroarylgroup, and the 8- to 10-membered fused heteroaryl group may optionallyhave one or more substituents selected from Group R^(4-4A), providedthat when they have two or more substituents, then the substituents maybe same or different; the Group R^(4-4A) consists of halogen, a cyanogroup, a nitro group, a formyl group, a C1-C6 alkyl group, a C1-C6alkoxy group, a (C1-C6 alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group,a C2-C6 alkynyl group, a C3-C6 cycloalkyl group, a C1-C6 alkylthiogroup, a C1-C6 alkylsulfinyl group, a C1-C6 alkylsulfonyl group, a C1-C6alkylamino gout), a di(C1-C6 alkyl)amino group, a C3-C6 cycloalkylaminogroup, a (C1-C6 alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonylgroup, a (C1-C6 alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonylgroup, a di(C1-C6 alkyl)aminocarbonyl group, a (C3-C6cycloalkylamino)carbonyl group, a tri(C1-C6 alkyl)silyl group, a C6-C10aryl group, and a 5- or 6-membered heteroaryl group; in the Group R⁴⁴A,the C1-C6 alkyl group, the C1-C6 alkoxy group, the (C1-C6 alkoxy)C1-C6alkyl group, the C2-C6 alkenyl group, the C2-C6 alkynyl group, the C3-C6cycloalkyl group, the C1-C6 alkylthio group, the C1-C6 alkylsulfinylgroup, the C1-C6 alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group,the (C3-C6 cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonylgroup may be optionally substituted with one or more halogens, providedthat when they are substituted with two or more halogens, then thehalogens may be same or different; and the C6-C10 aryl group and the 5-or 6-membered heteroaryl group may optionally have one or moresubstituents selected from Group 4-4A, provided that when they have twoor more substituents, then the substituents may be same or different;the Group 4-4A consists of halogen, a cyano group, a nitro group, aformyl group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a (C1-C6alkoxy)C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group,a C3-C6 cycloalkyl group, a C1-C6 alkylthio group, a C1-C6 alkylsulfinylgroup, a C1-C6 alkylsulfonyl group, a C1-C6 alkylamino mow, a di(C1-C6alkyl)amino group, a C3-C6 cycloalkylamino group, a (C1-C6alkyl)carbonyl group, a (C3-C6 cycloalkyl)carbonyl group, a (C1-C6alkoxy)carbonyl group, a (C1-C6 alkylamino)carbonyl group, a di(C1-C6alkyl)aminocarbonyl group, a (C3-C6 cycloalkylamino)carbonyl group, anda tri(C1-C6 alkyl)silyl group; in the Group 4-4A, the C1-C6 alkyl group,the C1-C6 alkoxy group, the (C1-C6 alkoxy)C1-C6 alkyl group, the C2-C6alkenyl group, the C2-C6 alkynyl group, the C3-C6 cycloalkyl group, theC1-C6 alkylthio group, the C1-C6 alkylsulfinyl group, the C1-C6alkylsulfonyl group, the (C1-C6 alkyl)carbonyl group, the (C3-C6cycloalkyl)carbonyl group, and the (C1-C6 alkoxy)carbonyl group may beoptionally substituted with one or more halogens, provided that whenthey are substituted with two or more halogens, then the halogens may besame or different; and n represents an integer of 0, 1 or
 2. 2. Thecompound according to claim 1, wherein G^(4A) is a phenyl group whereinthe phenyl group may optionally have one or more substituents selectedfrom the Group R^(4-4A), provided that when it has two or moresubstituents, then the substituents may be same or different.
 3. Thecompound according to claim 1, wherein the Group R^(4-4A) is GroupR^(4-4A-1); wherein the Group R^(4-4A-1) consists of halogen, a cyanogroup, a nitro group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group; in theGroup R^(4-4A-1), the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent; and the phenyl group may optionally have one or moresubstituents selected from Group 4-4A-1, provided that when it has twoor more substituents, then the substituents may be same or different;the Group 4-4A-1 consists of halogen and a C1-C6 alkyl group; in theGroup 4-4A-1, the C1-C6 alkyl group may be optionally substituted withone or more halogens, provided that when it is substituted with two ormore halogens, then the halogens may be same or different.
 4. Thecompound according to claim 3, wherein R^(2-4A) is hydrogen or a C1-C6alkyl group wherein the C1-C6 alkyl group may be optionally substitutedwith one or more halogens, provided that when it is substituted with twoor more halogens, then the halogens may be same or different; R^(3-4A)is hydrogen, a C1-C6 alkyl group, a (C1-C6 alkoxy)C1-C6 alkyl group, ora benzyl group wherein the C1-C6 alkyl group and the (C1-C6 alkoxy)C1-C6alkyl group may be optionally substituted with one or more halogens,provided that when they are substituted with two or more halogens, thenthe halogens may be same or different; and the benzyl group mayoptionally have one or more substituents selected from the groupconsisting of halogen, a C1-C6 alkyl group, and a C1-C6 alkoxy group,provided that when it has two or more substituents, then thesubstituents may be same or different; R^(5-4A) is a C1-C6 alkyl groupor a phenyl group wherein the C1-C6 alkyl group may be optionallysubstituted with one or more halogens, provided that when it issubstituted with two or more halogens, then the halogens may be same ordifferent; and the phenyl group has one or more C1-C6 alkyl groups,provided that when it has two or more C1-C6 alkyl groups, then the C1-C6alkyl groups may be same or different; and G^(4A) is a phenyl group, apyridyl group, an indolyl group or a pyrazolyl group wherein the phenylgroup, the pyridyl group, the indolyl group and the pyrazolyl group mayoptionally have one or more substituents selected from Group R^(4-4A-1),provided that when they have two or more substituents, then thesubstituents may be same or different.
 5. The compound according toclaim 1, wherein R^(2-4A) is a methyl group, a 4-fluorophenyl group or atrifluoromethyl group, R^(3-4A) is a methyl group or a benzyl group,R^(5-4A) is a methyl group or a 4-methylphenyl group, and G^(4A) is a2,4,6-triethylphenyl group, a 2-ethyl-5-(4-chlorophenyl)phenyl group, a5-ethyl-3-(4-trifluoromethylphenyl)pyrazol-1-yl group, a1-methylindol-3-yl group or a 2,6-diethyl-4-methylphenyl group.
 6. Thecompound according to claim 2, wherein the Group R^(4-4A) is GroupR^(4-4A-1); wherein the Group R^(4-4A-1) consists of halogen, a cyanogroup, a nitro group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group; in theGroup R^(4-4A-1), the C1-C6 alkyl group, the C1-C6 alkoxy group, theC3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionallysubstituted with one or more halogens, provided that when they aresubstituted with two or more halogens, then the halogens may be same ordifferent; and the phenyl group may optionally have one or moresubstituents selected from Group 4-4A-1, provided that when it has twoor more substituents, then the substituents may be same or different;the Group 4-4A-1 consists of halogen and a C1-C6 alkyl group; in theGroup 4-4A-1, the C1-C6 alkyl group may be optionally substituted withone or more halogens, provided that when it is substituted with two ormore halogens, then the halogens may be same or different.